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  • 1.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ekerot, Carl-Fredrik
    Department of Experimental Medical Sciences, Section for Neuroscience, Lund.
    The lateral reticular nucleus: a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.2013In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 591, no 22, p. 5453-5458Article in journal (Refereed)
    Abstract [en]

    The lateral reticular nucleus (LRN) is a major precerebellar centre of mossy fibre information to the cerebellum from the spinal cord that is distinct from the direct spinocerebellar paths. The LRN has traditionally been considered to provide the cerebellum with segregated information from several spinal systems controlling posture, reaching, grasping, locomotion, scratching and respiration. However, results are presented that show extensive convergence on a majority of LRN neurons from spinal systems. We propose a new hypothesis suggesting that the LRN may use extensive convergence from the different input systems to provide overview and integration of linked motor components to the cerebellum. This integrated information is sent in parallel with the segregated information from the individual systems to the cerebellum that finally may compare the activity and make necessary adjustments of various motor behaviours.

  • 2.
    Axelson, Hans W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Hagbarth, K -E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Human motor control consequences of thixotropic changes in muscular short-range stiffness2001In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 535, no Pt 1, p. 279-288Article in journal (Refereed)
    Abstract [en]
    1. The primary aim of the present study was to explore whether in healthy subjects the muscle contractions required for unrestrained voluntary wrist dorsiflexions are adjusted in strength to thixotropy-dependent variations in the short-range stiffness encountered in measurements of passive torque resistance to imposed wrist dorsiflexions.
    2. After a period of rest, only the first movement in a series of passive wrist dorsiflexions of moderate amplitude exhibited clear signs of short-range stiffness in the torque response. During analogous types of voluntary movements, the extensor EMG during the first movement after rest showed a steep initial rise of activity, which apparently served to compensate for the short-range stiffness.
    3. The passive torque resistance to minute repetitive wrist dorsiflexions (within the range of short-range stiffness) was markedly reduced after various types of mechanical agitation. During analogous low-amplitude voluntary wrist dorsiflexions the extensor EMG signals were weaker after than before agitation.
    4. Mechanical agitation also led to enhancement of passive dorsiflexion movements induced by weak constant torque pulses. In an analogous way, the movement-generating capacity of weak voluntary extensor activations (as determined by EMG recordings) was greatly enhanced by mechanical agitation.
    5. The signals from a force transducer probe pressed against the wrist flexor tendons - during passive wrist dorsiflexions - revealed short-range stiffness responses which highly resembled those observed in the torque measurements, suggesting that the latter to a large extent emanated from the stretched, relaxed flexor muscles. During repetitive stereotyped voluntary wrist dorsiflexions, a close correspondence was observed between the degree of short-range stiffness as sensed by the wrist flexor tension transducer and the strength of the initial extensor activation required for movement generation.
    6. The results provide evidence that the central nervous system in its control of voluntary movements takes account of and compensates for the history-dependent degree of inherent short-range stiffness of the muscles antagonistic to the prime movers.
  • 3.
    Barro-Soria, Rene
    et al.
    University of Miami, FL 33136 USA.
    Liin, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, H. Peter
    University of Miami, FL 33136 USA.
    Specificity of M-channel activators: binding or effect?2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 3, p. 605-606Article in journal (Other academic)
    Abstract [en]

    n/a

  • 4.
    Bengtsson, Per
    et al.
    Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden and the Department of Surgery and the Research Center, Karolinska Institute, Huddinge University Hospital, Sweden.
    Lundqvist, G.
    Department of Clinical Chemistry, Academic Hospital, Uppsala, Sweden.
    Nilsson, Göran
    Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden and the Department of Surgery and the Research Center, Karolinska Institute, Huddinge University Hospital, Sweden.
    Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands1989In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 419, p. 765-774Article in journal (Refereed)
    Abstract [en]

    1. The purpose of the present study was to investigate the role of somatostatin in the inhibition of acid production induced by caerulein and cholecystokinin (CCK) in isolated rabbit gastric glands. Acid production was estimated by the aminopyrine technique.

    2. Exogenous somatostatin 14 and somatostatin 28 (10(-7) M) reduced to a similar extent the aminopyrine uptake produced by 5 x 10(-5) M-histamine during the course of 40 min incubation.

    3. Significant inhibition of histamine-stimulated aminopyrine accumulation occurred at a somatostatin 14 concentration of 10(-9) M.

    4. Caerulein and CCK octapeptide (10(-13)-10(-7) M) were found to release somatostatin from isolated gastric glands in a dose-dependent manner. The dose-response relationships for somatostatin release and inhibition of aminopyrine uptake were similar. Thus, the half-maximal dose approximations for somatostatin release and inhibition of aminopyrine uptake were 0.5 and 1.4 x 10(-9) M respectively for CCK octapeptide and 0.9 and 2.5 x 10(-11) M for caerulein. Heptadecapeptide gastrin proved to be a very poor releaser of somatostatin in the system used. The CCK octapeptide-induced somatostatin release was time dependent and the concentrations of somatostatin that accumulated in the incubation medium were similar to those of exogenous somatostatin that were needed to evoke inhibition.

    5. The present results support the concept that cholecystokinin inhibits gastric acid secretion by releasing somatostatin from endocrine-like cells in the gastric mucosa. It is suggested that cholecystokinin-related peptides may play a physiological role in inhibiting gastric acid secretion. A similar role for gastrin is not supported by the present study.

  • 5. Bivol, Liliana Monica
    et al.
    Iversen, Bjarne Magnus
    Hultström, Michael
    Department of Clinical Science, University of Bergen, Norway.
    Wallace, Paal W
    Reed, Rolf Kåre
    Wiig, Helge
    Tenstad, Olav
    Unilateral renal ischemia in rats induces a rapid secretion of inflammatory markers to renal lymph and increased peritubular capillary permeability2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793Article in journal (Refereed)
    Abstract [en]

    A better understanding of the inflammatory process associated with renal ischemia-reperfusion (IR) injury may be clinically important. In this study we examined the role of the kidney in production of inflammatory mediators by analysing renal lymph after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion, as well as the effect of IR on size selectivity for proteins in both glomerular and peritubular capillaries. All measured mediators increased dramatically in renal hilar lymph, whereas plasma and renal cortical tissue samples returned to control levels after 120 min reperfusion. The responses were differentiated; Interleukin-1β, monocyte chemoattractant protein-1 and leptin were markedly increased in plasma before reperfusion, reflecting an extrarenal response possibly induced by afferent renal nerve activity from the ischemic kidney. Tumour necrosis factor-α  was the only mediator showing elevated lymph to plasma ratio following 30 min reperfusion, indicating that most cytokines were released directly into the bloodstream. The IR induced rise in cytokine levels was paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine. The latter was shown as a 14-166 fold increase in glomerular sieving coefficient of plasma proteins assessed by a novel proteomic approach, and indicated a temporarily reduced size selectivity of both glomerular and peritubular capillaries. Collectively, our data suggest that cytokines from the ischemic kidney explain most of the rise in plasma concentration, and that the locally produced substances enter the systemic circulation through transport directly to plasma and not via the interstitium to lymph.

  • 6.
    Blomstrand, Eva
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Rådegran, Göran
    Saltin, Bengt
    Maximum rate of oxygen uptake by human skeletal muscle in relation to maximal activities of enzymes in the Krebs cycle.1997In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 501 ( Pt 2), p. 455-60Article in journal (Refereed)
    Abstract [en]

    1. Ten subjects performed incremental exercise up to their maximum work rate with the knee extensors of one leg. Measurements of leg blood flow and femoral arteriovenous differences of oxygen were made in order to be able to calculate oxygen uptake of the leg. 2. The volume of the quadriceps muscle was determined from twenty-one to twenty-five computer tomography section images taken from the patella to the anterior inferior iliac spine of each subject. 3. The maximal activities of three enzymes in the Krebs cycle, citrate synthase, oxoglutarate dehydrogenase and succinate dehydrogenase, were measured in biopsy samples taken from the vastus lateralis muscle. 4. The average rate of oxygen uptake over the quadriceps muscle at maximal work, 353 ml min-1 kg-1, corresponded to a Krebs cycle rate of 4.6 mumol min-1 g-1. This was similar to the maximal activity of oxoglutarate dehydrogenase (5.1 mumol min-1 g-1), whereas the activities of succinate dehydrogenase and citrate synthase averaged 7.2 and 48.0 mumol min-1 g-1, respectively. 5. It is suggested that of these enzymes, only the maximum activity of oxoglutarate dehydrogenase can provide a quantitative measure of the capacity of oxidative metabolism, and it appears that the enzyme is fully activated during one-legged knee extension exercise at the maximal work rate.

  • 7.
    Blomstrand, Eva
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Saltin, Bengt
    Effect of muscle glycogen on glucose, lactate and amino acid metabolism during exercise and recovery in human subjects.1999In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 514 ( Pt 1), p. 293-302Article in journal (Refereed)
    Abstract [en]

    1. Eight subjects performed two-legged exercise, one leg with low and the other with normal muscle glycogen content. The purpose was to study the effect of low initial muscle glycogen content on the metabolic response during 1 h of exercise and 2 h of recovery. This model allows direct comparison of net fluxes of substrates and metabolites over the exercising legs receiving the same arterial inflow. 2. Muscle glycogen breakdown during exercise was 60% lower in the leg with a reduced pre-exercise glycogen concentration and the rate of glucose uptake during exercise was 30% higher. 3. The amount of pyruvate that was oxidized during exercise was calculated to be approximately 450 mmol in the low-glycogen leg and 750 mmol in the normal-glycogen leg, which suggests more fat and amino acid oxidation in the low-glycogen leg. 4. During exercise, there was a significant release of amino acids not metabolized in the muscle, e. g. tyrosine and phenylalanine, only from the low-glycogen leg, suggesting an increased rate of net protein degradation in this leg. 5. The release of tyrosine and phenylalanine from the low-glycogen leg during the exercise period and the change in their muscle concentrations yield a net tyrosine and phenylalanine production rate of 1.4 and 1.5 mmol h-1, respectively. The net rate of protein degradation was then calculated to be 7-12 g h-1. 6. The results suggest that the observed differences in metabolism between the low-glycogen and the normal-glycogen leg are induced by the glycogen level per se, since the legs received the same arterial supply of hormones and substrates.

  • 8. Bruton, Joseph D.
    et al.
    Aydin, Jan
    Yamada, Takashi
    Shabalina, Irina G.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Ivarsson, Niklas
    Zhang, Shi-Jin
    Wada, Masanobu
    Tavi, Pasi
    Nedergaard, Jan
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Katz, Abram
    Westerblad, Håkan
    Increased fatigue resistance linked to Ca(2+)-stimulated mitochondrial biogenesis in muscle fibres of cold-acclimated mice2010In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 588, no 21, p. 4275-4288Article in journal (Refereed)
    Abstract [en]

    Mammals exposed to a cold environment initially generate heat by repetitive muscle activity (shivering). Shivering is successively replaced by the recruitment of uncoupling protein-1 (UCP1)-dependent heat production in brown adipose tissue. Interestingly, adaptations observed in skeletal muscles of cold-exposed animals are similar to those observed with endurance training. We hypothesized that increased myoplasmic free [Ca2+] ([Ca2+]i) is important for these adaptations. To test this hypothesis, experiments were performed on flexor digitorum brevis (FDB) muscles, which do not participate in the shivering response, of adult wild-type (WT) and UCP1-ablated (UCP1-KO) mice kept either at room temperature (24 ºC) or cold-acclimated (4 ºC) for 4-5 weeks. [Ca2+]i (measured with indo-1) and force were measured under control conditions and during fatigue induced by repeated tetanic stimulation in intact single fibres. The results show no differences between fibres from WT and UCP1-KO mice. However, muscle fibres from cold-acclimated mice showed significant increases in basal [Ca2+]i (~50%), tetanic [Ca2+]i (~40%), and sarcoplasmic reticulum (SR) Ca2+ leak (~four-fold) as compared to fibres from room-temperature mice. Muscles of cold-acclimated mice showed increased expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and increased citrate synthase activity (reflecting increased mitochondrial content). Fibres of cold-acclimated mice were more fatigue resistant with higher tetanic [Ca2+]i and less force loss during fatiguing stimulation. In conclusion, cold exposure induces changes in FDB muscles similar to those observed with endurance training and we propose that increased [Ca2+]i is a key factor underlying these adaptations.

  • 9.
    Calbet, J A L
    et al.
    Department of Physical Education, University of Las Palmas de Gran Canaria, Spain.
    Jensen-Urstad, Mats
    van Hall, Gerrit
    Holmberg, H-C
    Rosdahl, Hans
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Saltin, Bengt
    Maximal muscular vascular conductances during whole body upright exercise in humans.2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 558, no Pt 1, p. 319-31Article in journal (Refereed)
    Abstract [en]

    That muscular blood flow may reach 2.5 l kg(-1) min(-1) in the quadriceps muscle has led to the suggestion that muscular vascular conductance must be restrained during whole body exercise to avoid hypotension. The main aim of this study was to determine the maximal arm and leg muscle vascular conductances (VC) during leg and arm exercise, to find out if the maximal muscular vasodilatory response is restrained during maximal combined arm and leg exercise. Six Swedish elite cross-country skiers, age (mean +/-s.e.m.) 24 +/- 2 years, height 180 +/- 2 cm, weight 74 +/- 2 kg, and maximal oxygen uptake (VO2,max) 5.1 +/- 0.1 l min(-1) participated in the study. Femoral and subclavian vein blood flows, intra-arterial blood pressure, cardiac output, as well as blood gases in the femoral and subclavian vein, right atrium and femoral artery were determined during skiing (roller skis) at approximately 76% of VO2max and at VO2max with different techniques: diagonal stride (combined arm and leg exercise), double poling (predominantly arm exercise) and leg skiing (predominantly leg exercise). During submaximal exercise cardiac output (26-27 l min(-1)), mean blood pressure (MAP) (approximately 87 mmHg), systemic VC, systemic oxygen delivery and pulmonary VO2(approximately 4 l min(-1)) attained similar values regardless of exercise mode. The distribution of cardiac output was modified depending on the musculature engaged in the exercise. There was a close relationship between VC and VO2 in arms (r= 0.99, P < 0.001) and legs (r= 0.98, P < 0.05). Peak arm VC (63.7 +/- 5.6 ml min(-1) mmHg(-1)) was attained during double poling, while peak leg VC was reached at maximal exercise with the diagonal technique (109.8 +/- 11.5 ml min(-1) mmHg(-1)) when arm VC was 38.8 +/- 5.7 ml min(-1) mmHg(-1). If during maximal exercise arms and legs had been vasodilated to the observed maximal levels then mean arterial pressure would have dropped at least to 75-77 mmHg in our experimental conditions. It is concluded that skeletal muscle vascular conductance is restrained during whole body exercise in the upright position to avoid hypotension.

  • 10. Calbet, José A L
    et al.
    Losa-Reyna, José
    Peralta, Rafael Torres
    Rasmussen, Peter
    Ponce-González, Jesús Gustavo
    Sheel, A William
    de la Calle-Herrero, Jaime
    Grau, Amelia Guadalupe
    Morales-Alamo, David
    Fuentes, Teresa
    Rodríguez-García, Lorena
    Siebenmann, Christoph
    Boushel, Robert
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Laboratory for Biomechanics and Motor Control.
    Lundby, Carsten
    Limitations to oxygen transport and utilisation during sprint exercise in humans: evidence for a functional reserve in muscle O2 diffusing capacity.2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 593, no 20, p. 4649-4664Article in journal (Refereed)
    Abstract [en]

    KEY POINTS SUMMARY: Severe acute hypoxia reduces sprint performance. Muscle VO2 during sprint exercise in normoxia is not limited by O2 delivery, O2 off-loading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle of young healthy men. A large functional reserve in muscle O2 diffusing capacity exists and remains available at exhaustion during exercise in normoxia, which is recruited during exercise in hypoxia. During whole-body incremental exercise to exhaustion in severe hypoxia leg VO2 is primarily dependent on convective O2 delivery and less limited by diffusion constraints than previously thought. The kinetics of O2 off-loading from haemoglobin does not limit VO2 peak in hypoxia. Our results indicate that the limitation to VO2 during short sprints resides in mechanisms regulating mitochondrial respiration.

    ABSTRACT: To determine the contribution of convective and diffusive limitations to VO2 peak during exercise in humans oxygen transport and haemodynamics were measured in eleven men (22 ± 2 years) during incremental (IE) and 30-s all-out sprints (Wingate test, WgT), in normoxia (Nx, PI O2 :143 mmHg) and hypoxia (Hyp, PI O2 :73 mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg VO2 was measured by the Fick method, and leg blood flow (BF) with thermodilution and muscle O2 diffusing capacity (DMO2 ) was calculated. In the WgT mean power output, leg BF, leg O2 delivery and leg VO2 were 7, 5, 28 and 23% lower in Hyp than Nx (P < 0.05), however, peak WgT DMO2 was higher in hypoxia (51.5 ± 9.7) than Nx (20.5 ± 3.0 ml min(-1) mmHg(-1) , P < 0.05). Despite a similar PaO2 (33.3 ± 2.4 and 34.1 ± 3.3 mmHg), mean capillary PO2 (16.7 ± 1.2 and 17.1 ± 1.6 mmHg), and peak perfusion during IE and WgT in Hyp, DMO2 and leg VO2 were 12 and 14% higher during WgT than IE in Hyp (both, P < 0.05). DMO2 was apparently insensitive to COHb (COHb: 0.7 vs 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O2 transfer both in Nx and Hyp. In conclusion, muscle VO2 during sprint exercise is not limited by O2 delivery, the O2 off-loading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O2 diffusing capacity. This article is protected by copyright. All rights reserved.

  • 11.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Impaired ribosome biogenesis could contribute to anabolic resistance to strength exercise in the elderly2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 5, p. 1447-1448Article, review/survey (Refereed)
  • 12. Charifi, N.
    et al.
    Kadi, Fawzi
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Féasson, L.
    Costes, F.
    Geyssant, A.
    Denis, C.
    Enhancement of microvessel tortuosity in the vastus lateralis muscle of old men in response to endurance training2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 554, no Pt 2, p. 559-569Article in journal (Refereed)
    Abstract [en]

    Muscle microvascularization is usually quantified in transverse sections, in absolute terms (capillaries around fibres, CAF, or capillary-to-fibre ratio, C/F) or as CAF related to fibre area (CAF/area, CAFA). The capillary-to-fibre perimeter exchange ratio (CFPE) has been introduced in order to assess the role of the capillary-to-fibre interface in resistance to O(2) diffusion. The ratio between the length of capillaries in contact with fibres and fibre perimeter (LC/PF) has also been used as an index for capillary tortuosity. The possibility of change in capillary tortuosity with endurance training was not considered in previous studies. Consequently, this study investigated the effect of 14 weeks of endurance training on muscle microvascularization, including microvessel tortuosity, in 11 elderly men (8th decade). Microvessels were analysed using the CD31 antibody. Together with the significant increase in peak oxygen exchange and citrate synthase activity, there was a significant increase in C/F. While CFPE and CAFA remained unchanged, an important finding was the clear increase in LC/PF (56%; P < 0.001) for a same sarcomere length. We also found a strong correlation between oxidative enzyme activity and LC/PF both before and after training. These results indicate that endurance training induces significant remodelling in the microvessel network in elderly men and that an increase in the degree of microvessel tortuosity would be an important mechanism of adaptation to endurance training.

  • 13.
    Cheng, Arthur
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Gineste, Charlotte
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Schlittler, Maja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Intracellular Ca(2+) handling and myofibrillar Ca(2+) sensitivity are defective in single muscle fibres of aged humans2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 593, no 15, p. 3237-3238Article in journal (Refereed)
  • 14.
    Cheng, Arthur J.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; School of Kinesiology and Health Sciences, York University, Toronto, Canada.
    Allodi, Ilary
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Schlittler, Maja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Ivarsson, Niklas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Thams, Sebastian
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hedlund, Eva
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Daniel C.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Theme; Section for Heart Failure, Arrhythmia and GUCH; Karolinska University Hospital, Stockholm, Sweden.
    Intact single muscle fibres from SOD1(G93A) amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training-like adaptations2019In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 597, no 12, p. 3133-3146Article in journal (Refereed)
    Abstract [en]

    Key points:

    • How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated.
    • Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force.
    • On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance.
    • These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype.

    Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125–150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+] ([Ca2+]i), and resting [Ca2+]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.

  • 15.
    Cheng, Arthur J.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden .
    Place, Nicolas
    Institute of Movement Sciences and Sports Medicine, Medicine Faculty, Geneva University, Geneva, Switzerland .
    Bruton, Joseph D.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden .
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Westerblad, Håkan
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden .
    Doublet discharge stimulation increases sarcoplasmic reticulum Ca2+ release and improves performance during fatiguing contractions in mouse muscle fibres2013In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 591, no 15, p. 3739-3748Article in journal (Refereed)
    Abstract [en]

    Double discharges (doublets) of motor neurones at the onset of contractions increase both force and rate of force development during voluntary submaximal contractions. The purpose of this study was to examine the role of doublet discharges on force and myoplasmic free [Ca2+] ([Ca2+](i)) during repeated fatiguing contractions, using a stimulation protocol mimicking the in vivo activation pattern during running. Individual intact fibres from the flexor digitorum brevis muscle of mice were stimulated at 33 degrees C to undergo 150 constant-frequency (five pulses at 70 Hz) or doublet (an initial, extra pulse at 200 Hz) contractions at 300 ms intervals. In the unfatigued state, doublet stimulation resulted in a transient (approximate to 10 ms) approximate doubling of [Ca2+](i), which was accompanied by a greater force-time integral (approximate to 70%) and peak force (approximate to 40%) compared to constant frequency contractions. Moreover, doublets markedly increased force-time integral and peak force during the first 25 contractions of the fatiguing stimulation. In later stages of fatigue, addition of doublets increased force production but the increase in force production corresponded to only a minor portion of the fatigue-induced reduction in force. In conclusion, double discharges at the onset of contractions effectively increase force production, especially in early stages of fatigue. This beneficial effect occurs without additional force loss in later stages of fatigue, indicating that the additional energy cost induced by doublet discharges to skeletal muscle is limited.

  • 16.
    Cheng, Arthur J.
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Willis, Sarah J.
    Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Zinner, Christoph
    Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Karolinska Institutet, Stockholm, Sweden.
    Ivarsson, Niklas
    Karolinska Institutet, Stockholm, Sweden.
    Ørtenblad, Niels
    University of Southern Denmark, Odense, Denmark.
    Lanner, Johanna T.
    Karolinska Institutet, Stockholm, Sweden.
    Holmberg, Hans-Christer
    Karolinska Institutet, Stockholm, Sweden; Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Westerblad, Håkan
    Karolinska Institutet, Stockholm, Sweden.
    Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 24, p. 7413-7426Article in journal (Refereed)
    Abstract [en]

    Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by two hours recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca(2+) ] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole FDB muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.

  • 17.
    Cheng, Arthur J.
    et al.
    Karolinska Institutet.
    Willis, Sarah J.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Zinner, Christoph
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Chaillou, Thomas
    Karolinska Institutet; Örebro universitet.
    Ivarsson, Niklas
    Karolinska Institutet.
    Ørtenblad, Niels
    University of Southern Denmark, Odense, Denmark.
    Lanner, Johanna T.
    Karolinska Institutet.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Karolinska Institutet.
    Westerblad, Håkan
    Karolinska Institutet.
    Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 24, p. 7413-7426Article in journal (Refereed)
    Abstract [en]

    Key points: We investigated whether intramuscular temperature affects the acute recovery of exercise performance following fatigue-induced by endurance exercise. Mean power output was better preserved during an all-out arm-cycling exercise following a 2 h recovery period in which the upper arms were warmed to an intramuscular temperature of ˜ 38°C than when they were cooled to as low as 15°C, which suggested that recovery of exercise performance in humans is dependent on muscle temperature. Mechanisms underlying the temperature-dependent effect on recovery were studied in intact single mouse muscle fibres where we found that recovery of submaximal force and restoration of fatigue resistance was worsened by cooling (16-26°C) and improved by heating (36°C). Isolated whole mouse muscle experiments confirmed that cooling impaired muscle glycogen resynthesis. We conclude that skeletal muscle recovery from fatigue-induced by endurance exercise is impaired by cooling and improved by heating, due to changes in glycogen resynthesis rate.

    Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by 2 h recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca2+] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole flexor digitorum brevis muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.

  • 18. Chow, R H
    et al.
    Lund, P-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Löser, S
    Panten, U
    Gylfe, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Coincidence of early glucose-induced depolarization with lowering of cytoplasmic Ca2+ in mouse pancreatic beta-cells1995In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 485, no 3, p. 607-617Article in journal (Refereed)
    Abstract [en]

    1. The temporal relationship between the early glucose-induced changes of membrane potential and cytoplasmic Ca2+ concentration ([Ca2+]i) was studied in insulin-releasing pancreatic beta-cells. 2. The mean resting membrane potential and [Ca2+]i were about -70 mV and 60 nM, respectively, in 3 mM glucose. 3. Elevating the glucose concentration to 8-23 mM typically elicited a slow depolarization, which was paralleled by a lowering of [Ca2+]i. When the slow depolarization had reached a threshold of -55 to -40 mV, there was rapid further depolarization to a plateau with superimposed action potentials, and [Ca2+]i increased dramatically. 4. Imposing hyperpolarizations and depolarizations of 10 mV from a holding potential of -70 mV had no detectable effect on [Ca2+]i. Furthermore, glucose elevation elicited a decrease in [Ca2+]i even at a holding potential of -70 mV. 5. Step depolarizations induced [Ca2+]i transients, which decayed with time courses well fitted by double exponentials. The slower component became faster by a factor of about 4 upon elevation of glucose, suggesting involvement of ATP-dependent Ca2+ sequestration or extrusion of [Ca2+]i. 6. Glucose stimulation increased the size and accelerated the recovery of carbachol-triggered [Ca2+]i transients, and thapsigargin, an intracellular Ca(2+)-ATPase inhibitor, counteracted the glucose-induced lowering of [Ca2+]i, indicating that calcium transport into intracellular stores is involved in glucose-induced lowering of [Ca2+]i. 7. The results support the notion that in beta-cells, nutrient-induced elevation of ATP leads initially to ATP-dependent removal of Ca2+ from the cytoplasm, paralleled by a slow depolarization due to inhibition of ATP-sensitive K+ channels. Only after depolarization has reached a threshold do action potentials occur, inducing a sharp elevation in [Ca2+]i.

  • 19. Corpeno Kalamgi, Rebeca
    et al.
    Salah, Heba
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Gastaldello, Stefano
    Martinez-Redondo, Vicente
    Ruas, Jorge
    Fury, Wen
    Bai, Yu
    Gromada, Jesper
    Sartori, Roberta
    Guttridge, Denis
    Sandri, Marco
    Larsson, Lars
    Mechano-signalling pathways in an experimental intensive critical illness myopathy model2016In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793Article in journal (Refereed)
  • 20. Corpeno Kalamgi, Rebeca
    et al.
    Salah, Heba
    Gastaldello, Stefano
    Martinez-Redondo, Vicente
    Ruas, Jorge L
    Fury, Wen
    Bai, Yu
    Gromada, Jesper
    Sartori, Roberta
    Guttridge, Denis C
    Sandri, Marco
    Larsson, Lars
    Mechano-signalling pathways in an experimental intensive critical illness myopathy model.2016In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 594, no 15, p. 4371-88Article in journal (Refereed)
    Abstract [en]

    KEY POINTS: Using an experimental rat intensive care unit (ICU) model, not limited by early mortality, we have previously shown that passive mechanical loading attenuates the loss of muscle mass and force-generation capacity associated with the ICU intervention. Mitochondrial dynamics have recently been shown to play a more important role in muscle atrophy than previously recognized. In this study we demonstrate that mitochondrial dynamics, as well as mitophagy, is affected by mechanosensing at the transcriptional level, and muscle changes induced by unloading are counteracted by passive mechanical loading. The recently discovered ubiquitin ligases Fbxo31 and SMART are induced by mechanical silencing, an induction that similarly is prevented by passive mechanical loading.

    ABSTRACT: The complete loss of mechanical stimuli of skeletal muscles, i.e. loss of external strain related to weight bearing and internal strain related to activation of contractile proteins, in mechanically ventilated, deeply sedated and/or pharmacologically paralysed intensive care unit (ICU) patients is an important factor triggering the critical illness myopathy (CIM). Using a unique experimental ICU rat model, mimicking basic ICU conditions, we have recently shown that mechanical silencing is a dominant factor triggering the preferential loss of myosin, muscle atrophy and decreased specific force in fast- and slow-twitch muscles and muscle fibres. The aim of this study is to gain improved understanding of the gene signature and molecular pathways regulating the process of mechanical activation of skeletal muscle that are affected by the ICU condition. We have focused on pathways controlling myofibrillar protein synthesis and degradation, mitochondrial homeostasis and apoptosis. We demonstrate that genes regulating mitochondrial dynamics, as well as mitophagy are induced by mechanical silencing and that these effects are counteracted by passive mechanical loading. In addition, the recently identified ubiquitin ligases Fbxo31 and SMART are induced by mechanical silencing, an induction that is reversed by passive mechanical loading. Thus, mechano-cell signalling events are identified which may play an important role for the improved clinical outcomes reported in response to the early mobilization and physical therapy in immobilized ICU patients.

  • 21.
    Corpeno, Rebeca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Dworkin, Barry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Cacciani, Nicola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Salah, Heba
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Bergman, Hilde-Marlene
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ravara, B
    Vitadello, M
    Gorza, Luisa
    Gustafson, Ann-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Hedström, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Petersson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Feng, H-Z
    Jin, Jian-Ping
    Iwamoto, Hiroyuki
    Yagi, Naoto
    Artemenko, Konstantin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Time-course analysis of mechanical ventilation-induced diaphragm contractile muscle dysfunction in the rat2014In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 592, no 17, p. 3859-3880Article in journal (Refereed)
    Abstract [en]

    Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive care unit (ICU) patients. To date, experimental and clinical studies have primarily focused on early effects on the diaphragm by CMV, or at specific time points. To improve our understanding of the mechanisms underlying the impaired diaphragm muscle function in response to mechanical ventilation, we have performed time‐resolved analyses between 6 h and 14 days using an experimental rat ICU model allowing detailed studies of the diaphragm in response to long‐term CMV. A rapid and early decline in maximum muscle fibre force and preceding muscle fibre atrophy was observed in the diaphragm in response to CMV, resulting in an 85% reduction in residual diaphragm fibre function after 9–14 days of CMV. A modest loss of contractile proteins was observed and linked to an early activation of the ubiquitin proteasome pathway, myosin:actin ratios were not affected and the transcriptional regulation of myosin isoforms did not show any dramatic changes during the observation period. Furthermore, small angle X‐ray diffraction analyses demonstrate that myosin can bind to actin in an ATP‐dependent manner even after 9–14 days of exposure to CMV. Thus, quantitative changes in muscle fibre size and contractile proteins are not the dominating factors underlying the dramatic decline in diaphragm muscle function in response to CMV, in contrast to earlier observations in limb muscles. The observed early loss of subsarcolemmal neuronal nitric oxide synthase activity, onset of oxidative stress, intracellular lipid accumulation and post‐translational protein modifications strongly argue for significant qualitative changes in contractile proteins causing the severely impaired residual function in diaphragm fibres after long‐term mechanical ventilation. For the first time, the present study demonstrates novel changes in the diaphragm structure/function and underlying mechanisms at the gene, protein and cellular levels in response to CMV at a high temporal resolution ranging from 6 h to 14 days.

  • 22. Druzin, M
    et al.
    Haage, D
    Malinina, Evgenya
    Johansson, S
    Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 542, no 1, p. 131-146Article in journal (Refereed)
  • 23.
    Druzin, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals.2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 542, no Pt 1, p. 131-46Article in journal (Refereed)
    Abstract [en]

    Calcium influx into the presynaptic nerve terminal is well established as a trigger signal for transmitter release by exocytosis. By studying dissociated preoptic neurons with functional adhering nerve terminals, we here show that presynaptic Ca2+ influx plays dual and opposing roles in the control of spontaneous transmitter release. Thus, application of various Ca2+ channel blockers paradoxically increased the frequency of spontaneous (miniature) inhibitory GABA-mediated postsynaptic currents (mIPSCs). Similar effects on mIPSC frequency were recorded upon washout of Cd2+ or EGTA from the external solution. The results are explained by a model with parallel Ca2+ influx through channels coupled to the exocytotic machinery and through channels coupled to Ca2+-activated K+ channels at a distance from the release site.

  • 24.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Cutaneous afferents provide information about knee joint movements in humans.2001In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 531, no Pt 1, p. 289-297Article in journal (Refereed)
    Abstract [en]

    1. Neurophysiological evidence that afferent information from skin receptors is important for proprioception has been gathered mainly in experiments relating to the human hand and finger joints. To investigate if proprioceptive information is also provided by skin mechanoreceptor afferents from skin areas related to large joints of postural importance, microneurography recordings were obtained in humans from skin afferents in the lateral cutaneous femoral nerve to study their responses to knee joint movements. 2. Data were collected from 60 sequentially recorded afferents from slowly (n = 23) and fast (n = 6) adapting low-threshold mechanoreceptors, hair follicle receptors (n = 24), field receptors (n = 1) and C mechanoreceptors (n = 6). Fascicular recordings showed that the lateral cutaneous femoral nerve supplies extensive areas of the thigh: from 5-10 cm below the inguinal ligament down to below and lateral to the knee joint; accordingly, the afferents originated in receptors located in wide areas of the human thigh. 3. All afferents from fast and slowly adapting low-threshold mechanoreceptors, as well as C mechanoreceptors, responded to manually applied skin stretch. In contrast, the same stimulus elicited, at most, feeble responses in hair follicle receptors. 4. Qualitative and quantitative analyses of the responses of a subset of afferents revealed that in particular slowly adapting afferents effectively encode both static and dynamic aspects of passively imposed knee joint movements. 5. It was concluded that receptors in the hairy skin of humans can provide high-fidelity information about knee joint movements. A previously undefined type of slowly adapting receptor (SA III) seemed particularly suited for this task whereas this does not seem to be the case for either hair follicle receptors or C mechanoreceptors.

  • 25.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Niclas
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Skin strain patterns provide kinaesthetic information to the human central nervous system.1995In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 487, no 1, p. 243-251Article in journal (Refereed)
    Abstract [en]

    1. We investigated the contribution of skin strain-related sensory inputs to movement perception and execution in five normal volunteers. The dorsal and palmar skin of the middle phalanx and the proximal interphalangeal (PIP) joint were manipulated to generate specific strain patterns in the proximal part of the index finger. To mask sensations directly related to this manipulation, skin and deeper tissues were blocked distal to the mid-portion of the proximal phalanx of the index finger by local anaesthesia. 2. Subjects were asked to move their normal right index finger either to mimic any perceived movements of the anaesthetized finger or to touch the tip of the insentient finger. 3. All subjects readily reproduced actual movements induced by the experimenter at the anaesthetized PIP joint. However, all subjects also generated flexion movements when the experimenter did not induce actual movement but produced deformations in the sentient proximal skin that were similar to those observed during actual PIP joint flexion. Likewise, the subjects indicated extension movement at the PIP joint when strain patterns corresponding to extension movements were induced. 4. In contrast, when the skin strain in the proximal part of the index finger was damped by a ring applied just proximal to the PIP joint within the anaesthetized skin area, both tested subjects failed to perceive PIP movements that actually took place.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 26.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Vallbo, A B
    Stretch sensitization of human muscle spindles.1988In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 400, p. 101-11Article in journal (Refereed)
    Abstract [en]

    1. Sixty-seven afferents from the finger extensor muscles were consecutively recorded by microneurography. 2. The units were classified as primary or secondary muscle spindle afferents or Golgi tendon organ afferents on the basis of their responses to ramp-and-hold stretches, sinusoidals superimposed on ramp-and-hold stretches, maximal twitch contractions and isometric contractions and relaxations. 3. The muscle was repeatedly stretched and then either kept short or long for a few seconds followed by a slow ramp stretch. The responses of the muscle afferents to the slow stretch were compared under the two conditions. 4. Thirty out of thirty-eight units classified as primary spindle afferents and four out of eleven units classified as secondary afferents showed an enhanced response to the slow ramp when the muscle had been kept short compared to the response when the muscle had been kept long. 5. None of the eighteen Golgi tendon organ afferents showed any difference in this respect. 6. It is concluded that stretch sensitization does occur in human muscle spindles and, when present, constitutes firm evidence of the afferent originating from a muscle spindle rather than a Golgi tendon organ. In addition, due to differences in the response characteristics of primaries and secondaries, the test may aid in separating muscle spindle primary afferents from secondary afferents.

  • 27.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Independent control of human finger-tip forces at individual digits during precision lifting.1992In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 450, p. 547-64Article in journal (Refereed)
    Abstract [en]

    1. Subjects lifted an object with two parallel vertical grip surfaces and a low centre of gravity using the precision grip between the tips of the thumb and index finger. The friction between the object and the digits was varied independently at each digit by changing the contact surfaces between lifts. 2. With equal frictional conditions at the two grip surfaces, the finger-tip forces were about equal at the two digits, i.e. similar vertical lifting forces and grip forces were used. With different frictions, the digit touching the most slippery surface exerted less vertical lifting force than the digit in contact with the rougher surface. Thus, the safety margins against slips were similar at the two digits whether they made contact with surfaces of similar or different friction. 3. During digital nerve block, large and variable safety margins were employed, i.e. the finger-tip forces did not reflect the surface conditions. Slips occurred more frequently than under normal conditions (14% of all trials with nerve block, <5% during normal conditions), and they only occasionally elicited compensatory adjustments of the finger-tip forces and then at prolonged latencies. 4. The partitioning of the vertical lifting force between the digits was thus dependent on digital afferent inputs and resulted from active automatic regulation and not just from the mechanics of the task. 5. The safety margin employed at a particular digit was mainly determined by the frictional conditions encountered by the digit, and to a lesser degree by the surface condition at the same digit in the previous lift (anticipatory control), but was barely influenced by the surface condition at the other digit. 6. It was concluded that the finger-tip forces were independently controlled for each digit according to a 'non-slip strategy'. The findings suggest that the force distribution among the digits represents a digit-specific lower-level neural control establishing a stable grasp. This control relies on digit-specific afferent inputs and somatosensory memory information. It is apparently subordinated to a higher-level control that is related to the total vertical lifting and normal forces required by the lifting task and the relevant physical properties of the manipulated object.

  • 28. Eghbali, Mansoureh
    et al.
    Birnir, Bryndis
    Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University.
    Gage, Peter W
    Conductance of GABAA channels activated by pentobarbitone in hippocampal neurons from newborn rats.2003In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 552, no Pt 1, p. 13-22Article in journal (Refereed)
    Abstract [en]

    Neurons were obtained from the CA1 region of the hippocampus of newborn rats and maintained in culture. Channels were activated by pentobarbitone in cell-attached, inside-out or outside-out patches, normally by applying pentobarbitone in flowing bath solution. Currents were outwardly rectifying and blocked by bicuculline, properties of GABAA channels in these cells. Maximum channel conductance increased as pentobarbitone concentration was increased to 500 microM but conductance then decreased as pentobarbitone concentration was raised further. The best fit of a Hill-type equation to the relationship between maximum channel conductance and pentobarbitone concentration (up to 500 microM) gave an EC50 of 41 microM, a maximum conductance of 36 pS and a Hill coefficient of 1.6. Bicuculline decreased the maximum conductance of the channels activated by pentobarbitone, with an IC50 of 224 microM. Diazepam increased channel conductance, with a maximum effect being obtained with 1 microM diazepam. Diazepam (1 microM) decreased the EC50 of the pentobarbitone effect on channel conductance from 41 microM to 7.2 microM and increased maximum conductance to 72 pS. We conclude that GABAA channel conductance is related to the concentration of the allosteric agonist pentobarbitone.

  • 29.
    Elinder, Fredrik
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Männikkö, Roope
    Pandey, Shilpi
    Larsson, H Peter
    Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels2006In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 575, no 2, p. 417-431Article in journal (Refereed)
    Abstract [en]

    Hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channels regulate pacemaker activity in the heart and the brain. Previously, we showed that spHCN and HCN1 channels undergo mode shifts in their voltage dependences, shifting the conductance versus voltage curves by more than +50 mV when measured from a hyperpolarized potential compared to a depolarized potential. In addition, the kinetics of the ionic currents changed in parallel to these voltage shifts. In the studies reported here, we tested whether slower cardiac HCN channels also display similar mode shifts. We found that HCN2 and HCN4 channels expressed in oocytes from the frog Xenopus laevis do not display the activation kinetic changes that we observed in spHCN and HCN1. However, HCN2 and HCN4 channels display changes in their tail currents, suggesting that these channels also undergo mode shifts and that the conformational changes underlying the mode shifts are due to conserved aspects of HCN channels. With computer modelling, we show that in channels with relatively slow opening kinetics and fast mode-shift transitions, such as HCN2 and HCN4 channels, the mode shift effects are not readily observable, except in the tail kinetics. Computer simulations of sino-atrial node action potentials suggest that the HCN2 channel, together with the HCN1 channel, are important regulators of the heart firing frequency and that the mode shift is an important property to prevent arrhythmic firing. We conclude that although all HCN channels appear to undergo mode shifts -and thus may serve to prevent arrhythmic firing -it is mainly observable in ionic currents from HCN channels with faster kinetics. 2006 The Authors. Journal compilation © 2006 The Physiological Society.

  • 30. Farmer, Adam D
    et al.
    Ban, Vin F
    Coen, Steven J
    Sanger, Gareth J
    Barker, Gareth J
    Gresty, Michael A
    Giampietro, Vincent P
    Williams, Steven C
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hellström, Per M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Andrews, Paul L R
    Aziz, Qasim
    Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 593, no 5, p. 1183-1196Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: Nausea is a highly individual and variable experience. The reasons for this variability are incompletely understood although psychophysiological factors have been proposed. Herein we describe objective psychophysiological changes induced by the subjective sensation of motion sickness. In comparison to subjects who did not develop nausea, nausea-sensitive subjects demonstrated electrogastrographic and autonomic changes, which included an increase in sympathetic nervous system activity with a concomitant reduction in parasympathetic activity. Furthermore, differences were also evident in plasma ghrelin, and subcortical and cortical activity. These data have a number of important implications for future research examining the physiological mechanisms that underlie nausea: ○The physiological, hormonal and cortical patterns identified herein represent potential biomarkers of the physiological mechanisms of nausea. ○Reverse translation of the physiological factors identified may facilitate refinement of animal models used to investigate novel anti-emetic agents and emetic liability of candidate drugs, increasing their validity and translation of finding to humans.

    ABSTRACT: An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions.

  • 31.
    Fernström, Maria
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle.2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 554, p. 755-763Article in journal (Refereed)
    Abstract [en]

    Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P < 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.

  • 32. Fernström, Maria
    et al.
    Tonkonogi, Michail
    Dalarna University, School of Health and Social Studies, Medical Science.
    Sahlin, Kent
    Effects of acute and chronic exercise on mitochondrial uncoupling in human skeletal muscle2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 554, no 3, p. 755-763Article in journal (Refereed)
    Abstract [en]

    Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of ) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training , citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P< 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.

  • 33.
    Gejl, Kasper D.
    et al.
    Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Odense, Denmark.
    Ørtenblad, Niels
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Univ Southern Denmark, Denmark.
    Andersson, Erik
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Plomgaard, Peter
    Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Swedish Olymp Comm, Stockholm.
    Nielsen, Joachim
    Department of Pathology, SDU Muscle Research Cluster, Odense University Hospital, Odense.
    Local depletion of glycogen with supra-maximal exercise in human skeletal muscle fibres2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 9, p. 2809-2821Article in journal (Refereed)
    Abstract [en]

    Skeletal muscle glycogen is heterogeneous distributed in three separated compartments (intramyofibrillar, intermyofibrillar and subsarcolemmal). Although only constituting 4-15% of the total glycogen volume, the availability of intramyofibrillar glycogen has been shown to be of particular importance to muscle function. The present study was designed to investigate the depletion of these three sub-cellular glycogen compartments during repeated supra-maximal exercise in elite athletes. Ten elite cross-country skiers (age: 25 +/- 4 yrs., VO2 max : 65 +/- 4 ml kg-1 min-1 , mean +/- SD) performed four approximately 4-minute supra-maximal sprint time trials (STT 1-4) with 45 min recovery. The sub-cellular glycogen volumes in m. triceps brachii were quantified from electron microscopy images before and after both STT 1 and STT 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in type I fibres (-52% [-89:-15%]) than type 2 fibres (-15% [-52:22%]) (P = 0.02), while the depletion of intermyofibrillar glycogen (main effect: -19% [-33:0], P = 0.006) and subsarcolemmal glycogen (main effect: -35% [-66:0%], P = 0.03) was similar between fibre types. In contrast, only intermyofibrillar glycogen volume was significantly reduced during STT 4, in both fibre types (main effect: -31% [-50:-11%], P = 0.002). Furthermore, for each of the sub-cellular compartments, the depletion of glycogen during STT 1 was associated with the volumes of glycogen before STT 1. In conclusion, the depletion of spatially distinct glycogen compartments differs during supra-maximal exercise. Furthermore, the depletion changes with repeated exercise and is fibre type-dependent. 

  • 34.
    Granseth, Björn
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Dynamic properties of corticogeniculate excitatory transmission in the rat dorsal lateral geniculate nucleus in vitro2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 556, no 1, p. 135-146Article in journal (Refereed)
    Abstract [en]

    The feedback excitation from the primary visual cortex to principal cells in the dorsal lateral geniculate nucleus (dLGN) is markedly enhanced with firing frequency. This property presumably reflects the ample short-term plasticity at the corticogeniculate synapse. The present study aims to explore corticogeniculate excitatory postsynaptic currents (EPSCs) evoked by brief trains of stimulation with whole-cell patch-clamp recordings in dLGN slices from DA-HAN rats. The EPSCs rapidly increased in amplitude with the first two or three impulses followed by a more gradual growth. A double exponential function with time constants 39 and 450 ms empirically described the growth for 5–25Hz trains. For lower train frequencies (down to 1Hz) a third component with time constant 4.8 s had to be included. The different time constants are suggested to represent fast and slow components of facilitation and augmentation. The time constant of the fast component changed with the extracellular calcium ion concentration as expected for a facilitation mechanism involving an endogenous calcium buffer that is more efficiently saturated with larger calcium influx. Concerning the function of the corticogeniculate feedback pathway, the different components of short-term plasticity interacted to increase EPSC amplitudes on a linear scale to firing frequency in the physiological range. This property makes the corticogeniculate synapse well suited to function as a neuronal amplifier that enhances the thalamic transfer of visual information to the cortex.

  • 35.
    Granseth, Björn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Ahlstrand, Erik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Paired pulse facilitation of corticogeniculate EPSCs in the dorsal lateral geniculate nucleus of the rat investigated in vitro2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 544, no 2, p. 477-486Article in journal (Refereed)
    Abstract [en]

    To investigate paired pulse facilitation of corticogeniculate EPSCs, whole-cell patch-clamp recordings were made from principal cells in the rat dorsal lateral geniculate nucleus (dLGN) in vitro. Thalamic slices, oriented so that both corticogeniculate and retinogeniculate axons could be stimulated, were cut from young (16- to 37-day-old) DA-HAN rats. Corticogeniculate EPSCs displayed pronounced paired pulse facilitation at stimulus intervals up to 400 ms. The facilitation had a fast and a slow component of decay with time constants of 12 ± 7 and 164 ± 47 ms (means ± s.d.), respectively. Maximum paired pulse ratio (EPSC2 × EPSC1−1) was 3.7 ± 1.1 at the 20-30 ms interval. Similar to other systems, the facilitation was presynaptic. Retinogeniculate EPSCs recorded in the same dLGN cells displayed paired pulse depression at intervals up to at least 700 ms. The two types of EPSCs differed in their calcium response curves. At normal [Ca2+]o, the corticogeniculate synapse functioned over the early rising part of a Hill function, while the retinogeniculate synapse operated over the middle and upper parts of the curve. The paired pulse ratio of corticogeniculate EPSCs was maximal at physiological [Ca2+]o. The facilitation is proposed to have an important role in the function of the corticogeniculate circuit as a neuronal amplifier.

  • 36.
    Granseth, Björn
    et al.
    MRC Laboratory of Molecular Biology, Cambridge.
    Lagnado, Leon
    MRC Laboratory of Molecular Biology, Cambridge.
    The role of endocytosis in regulating the strength of hippocampal synapses2008In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 586, p. 5969-5982Article in journal (Refereed)
    Abstract [en]

    The readily releasable pool of vesicles (RRP) varies in size during synaptic activity and is replenished by recruitment from the reserve pool as well as vesicle retrieval after fusion. To investigate which of these steps is rate limiting in supplying vesicles to the RRP, we measured the effects of changes in temperature in cultured hippocampal neurons, where higher average rates of release can be maintained as the temperature is increased. Using a pHluorin-based reporter of exocytosis and endocytosis (sypHy), we find that changes in temperature between 25 degrees C and 35 degrees C do not significantly alter the rate of recruitment from the reserve pool. In contrast, the time constant of endocytosis fell from approximately 17 s at 25 degrees C to approximately 10 s at 35 degrees C (Q(10) = 1.7), while the time constant of vesicle reacidification fell from approximately 5.5 s to approximately 1 s (Q(10) = 5.5). A kinetic model of the vesicle cycle constructed using measured parameters was found to describe variations in vesicle release rate observed during long trains of spikes as well as recovery from synaptic depression after bursts of activity. These results indicate that endocytosis operating with time constants of 10-15 s is the rate-limiting process determining replenishment of the RRP during long-term activity. A fast mode of vesicle retrieval could not be detected at any temperature, nor was it necessary to invoke such a mechanism to account for use-dependent changes in synaptic release probability.

  • 37.
    Granseth, Björn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Augmentation of corticogeniculate EPSCs in principal cells of the dorsal lateral geniculate nucleus of the rat investigated in vitro2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 556, no 1, p. 147-157Article in journal (Refereed)
    Abstract [en]

    Augmentation is a component of short-term synaptic plasticity with a gradual onset and duration in seconds. To investigate this component at the corticogeniculate synapse, whole cell patch-clamp recordings were obtained from principal cells in a slice preparation of the rat dorsal lateral geniculate nucleus. Trains with 10 stimuli at 25 Hz evoked excitatory postsynaptic currents (EPSCs) that grew in amplitude, primarily from facilitation. Such trains also induced augmentation that decayed exponentially with a time constant τ= 4.6 ± 2.6 s (mean ± standard deviation). When the trains were repeated at 1–10 s intervals, augmentation markedly increased the size of the first EPSCs, leaving late EPSCs unaffected. The magnitude of augmentation was dependent on the number of pulses, pulse rate and intervals between trains. Augmented EPSCs changed proportionally to basal EPSC amplitudes following alterations in extracellular calcium ion concentration. The results indicate that augmentation is determined by residual calcium remaining in the presynaptic terminal after repetitive spikes, competing with fast facilitation. We propose that augmentation serves to maintain a high synaptic strength in the corticogeniculate positive feedback system during attentive visual exploration.

  • 38.
    Granseth, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Odermatt, Benjamin
    MRC-LMB, Cambridge.
    Royle, Stephen J
    MRC-LMB, Cambridge.
    Lagnado, Leon
    MRC-LMB, Cambridge.
    Clathrin-mediated endocytosis: the physiological mechanism of vesicle retrieval at hippocampal synapses2007In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 585, no 3, p. 681-686Article, review/survey (Refereed)
    Abstract [en]

    The maintenance of synaptic transmission requires that vesicles are recycled after releasing neurotransmitter. Several modes of retrieval have been proposed to operate at small synaptic terminals of central neurons, but the relative importance of these has been controversial. It is established that synaptic vesicles can collapse on fusion and the machinery for retrieving this membrane by clathrin-mediated endocytosis (CME) is enriched in the presynaptic terminal. But it has also been suggested that the majority of vesicles released by physiological stimulation are recycled by a second, faster mechanism called 'kiss-and-run', which operates in 1 s or less to retrieve a vesicle before it has collapsed. The most recent evidence argues against the occurrence of 'kiss-and-run' in hippocampal synapses. First, an improved fluorescent reporter of exocytosis (sypHy), indicates that only a slow mode of endocytosis (tau = 15 s) operates when vesicle fusion is triggered by a single nerve impulse or short burst. Second, this retrieval mechanism is blocked by overexpressing the C-terminal fragment of AP180 or by knockdown of clathrin using RNAi. Third, vesicle fusion is associated with the movement of clathrin and vesicle proteins out of the synapse into the neighbouring axon. These observations indicate that clathrin-mediated endocytosis is the major, if not exclusive, mechanism of retrieval in small hippocampal synapses.

  • 39. Göpel, S
    et al.
    Kanno, T
    Barg, S
    Galvanovskis, J
    Rorsman, P
    Voltage-gated and resting membrane currents recorded from B-cells in intact mouse pancreatic islets.1999In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 521 Pt 3, p. 717-28Article in journal (Refereed)
    Abstract [en]

    1. The perforated patch whole-cell configuration of the patch-clamp technique was applied to superficial cells in intact pancreatic islets. Immunostaining in combination with confocal microscopy revealed that the superficial cells consisted of 35 % insulin-secreting B-cells and 65 % non-B-cells (A- and D-cells). 2. Two types of cell, with distinct electrophysiological properties, could be functionally identified. One of these generated oscillatory electrical activity when the islet was exposed to 10 mM glucose and had the electrophysiological characteristics of isolated B-cells maintained in tissue culture. 3. The Ca2+ current recorded from B-cells in situ was 80 % larger than that of isolated B-cells. It exhibited significant (70 %) inactivation during 100 ms depolarisations. The inactivation was voltage dependent and particularly prominent during depolarisations evoking the largest Ca2+ currents. 4. Voltage-dependent K+ currents were observed during depolarisations to membrane potentials above -20 mV. These currents inactivated little during a 200 ms depolarisation and were unaffected by varying the holding potential between -90 and -30 mV. 5. The maximum resting conductance in the absence of glucose, which reflects the conductance of ATP-regulated K+ (KATP) channels, amounted to approximately 4 nS. Glucose produced a concentration-dependent reduction of KATP channel conductance with half-maximal inhibition observed with 5 mM glucose. 6. Combining voltage- and current-clamp recording allowed the estimation of the gap junction conductance between different B-cells. These experiments indicated that the input conductance of the B-cell at stimulatory glucose concentrations ( approximately 1 nS) is almost entirely accounted for by coupling to neighbouring B-cells.

  • 40. Göpel, S O
    et al.
    Kanno, T
    Barg, S
    Rorsman, P
    Patch-clamp characterisation of somatostatin-secreting -cells in intact mouse pancreatic islets.2000In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 528, no Pt 3, p. 497-507Article in journal (Refereed)
    Abstract [en]

    The perforated patch whole-cell configuration of the patch-clamp technique was applied to superficial cells in intact mouse pancreatic islets. Three types of electrical activity were observed corresponding to alpha-, beta- and delta-cells. The delta-cells were electrically active in the presence of glucose but lacked the oscillatory pattern seen in the beta-cells. By contrast, the alpha-cells were electrically silent at high glucose concentrations but action potentials could be elicited by removal of the sugar. Both alpha- and beta-cells contained transient voltage-activated K+ currents. In the delta-cells, the K+ currents activated above -20 mV and were completely blocked by TEA (20 mM). The alpha-cells differed from the delta-cells in possessing a TEA-resistant K+ current activating already at -40 mV. Immunocytochemistry revealed the presence of Kv3.4 channels in delta-cells and TEA-resistant Kv4.3 channels in alpha-cells. Thus the presence of a transient TEA-resistant current can be used to functionally separate the delta- and alpha-cells. A TTX-sensitive Na+ current developed in delta-cells during depolarisations beyond -30 mV and reached a peak amplitude of 350 pA. Steady-state inactivation of this current was half-maximal at -28 mV. The delta-cells were also equipped with a sustained Ca2+ current that activated above -30 mV and reached a peak of 60 pA when measured at 2.6 mM extracellular Ca2+. A tolbutamide-sensitive KATP channel conductance was observed in delta-cells exposed to glucose-free medium. Addition of tolbutamide (0.1 mM) depolarised the delta-cell and evoked electrical activity. We propose that the KATP channels in delta-cells serve the same function as in the beta-cell and couple an elevation of the blood glucose concentration to stimulation of hormone release.

  • 41. Göpel, S O
    et al.
    Kanno, T
    Barg, S
    Weng, X G
    Gromada, J
    Rorsman, P
    Regulation of glucagon release in mouse -cells by KATP channels and inactivation of TTX-sensitive Na+ channels.2000In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 528, no Pt 3, p. 509-20Article in journal (Refereed)
    Abstract [en]

    The perforated patch whole-cell configuration of the patch-clamp technique was applied to superficial glucagon-secreting alpha-cells in intact mouse pancreatic islets. alpha-cells were distinguished from the beta- and delta-cells by the presence of a large TTX-blockable Na+ current, a TEA-resistant transient K+ current sensitive to 4-AP (A-current) and the presence of two kinetically separable Ca2+ current components corresponding to low- (T-type) and high-threshold (L-type) Ca2+ channels. The T-type Ca2+, Na+ and A-currents were subject to steady-state voltage-dependent inactivation, which was half-maximal at -45, -47 and -68 mV, respectively. Pancreatic alpha-cells were equipped with tolbutamide-sensitive, ATP-regulated K+ (KATP) channels. Addition of tolbutamide (0.1 mM) evoked a brief period of electrical activity followed by a depolarisation to a plateau of -30 mV with no regenerative electrical activity. Glucagon secretion in the absence of glucose was strongly inhibited by TTX, nifedipine and tolbutamide. When diazoxide was added in the presence of 10 mM glucose, concentrations up to 2 microM stimulated glucagon secretion to the same extent as removal of glucose. We conclude that electrical activity and secretion in the alpha-cells is dependent on the generation of Na+-dependent action potentials. Glucagon secretion depends on low activity of KATP channels to keep the membrane potential sufficiently negative to prevent voltage-dependent inactivation of voltage-gated membrane currents. Glucose may inhibit glucagon release by depolarising the alpha-cell with resultant inactivation of the ion channels participating in action potential generation.

  • 42.
    Göransson, Viktoria
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Johnsson, Cecilia
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Nylander, Olof
    Uppsala University, Department of Comparative Medicine. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Hansell, Peter
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
    Renomedullary and intestinal hyaluronan content during body water excess: a study in rats and gerbils2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 542, no 1, p. 315-22Article in journal (Refereed)
    Abstract [en]

    Our previous studies in rats have suggested a role for renomedullary hyaluronan (HA) in water homeostasis. The gerbil is known for its unique ability to conserve water. In the present study renal papillary and intestinal HA were compared between groups of anaesthetized gerbils and rats before and after up to 6 h of I.V. water loading. Baseline papillary HA in gerbils was only 37 % of that in the rat. Water loading in rats increased the papillary HA content. Elevation was maximal (+27 %, P < 0.05) after 2 h of water loading and then declined to control levels after 6 h of water loading (+3 %, n.s.). In contrast, the gerbil responded with a decreased papillary HA content during water loading. The depression was maximal after 2 h (-49 %, P < 0.05) and was still 41 % below the control values after 6 h (P < 0.05). The urine flow rate increased rapidly in the rat and its maximum, 21 times above the control level (P < 0.05), occurred at the HA peak, i.e. after 2 h of water loading while in the gerbil, the urine flow rate increased slowly and slightly and was only six times above control values after 6 h of water loading (P < 0.05). The HA content along the intestine was similar in the two species: lowest in the duodenum and jejunum and highest in the distal colon. To conclude, in the rat, the elevation of papillary interstitial HA during acute water loading would counteract water reabsorption by changing the physico-chemical characteristics of the interstitial matrix favouring rapid water diuresis. This would work as a complement to the powerful regulation by ADH. The gerbil has a diametrically different regulation of papillary HA turnover during water loading. The decreased papillary HA level during water loading and the slow and small diuretic response may represent a genetic difference in adaptation to enhance the ability to conserve water in an arid environment.

  • 43.
    Hostrup, M.
    et al.
    Department of Nutrition, Exercise and Sports, Section of Integrated Physiology, University of Copenhagen, Denmark .
    Kalsen, A.
    Department of Nutrition, Exercise and Sports, Section of Integrated Physiology, University of Copenhagen, Denmark .
    Ørtenblad, Niels
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Department of Sports Science and Biomechanics, University of Southern Denmark, Denmark .
    Juel, C.
    Department of Biology, University of Copenhagen, Denmark .
    Mørch, K.
    Department of Nutrition, Exercise and Sports, Section of Integrated Physiology, University of Copenhagen, Denmark .
    Rzeppa, S.
    Norwegian Doping Control Laboratory, Oslo University Hospital, Norway .
    Karlsson, S.
    Department of Respiratory Research, Bispebjerg University Hospital, Denmark .
    Backer, V.
    Department of Respiratory Research, Bispebjerg University Hospital, Denmark .
    Bangsbo, J.
    Department of Nutrition, Exercise and Sports, Section of Integrated Physiology, University of Copenhagen, Denmark .
    β2-Adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+-K+-ATPase Vmax in trained men2014In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 592, no 24, p. 5445-5459Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to examine the effect of β2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca2+ release and uptake, and Na+-K+-ATPase activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 males, EXP2, n = 20 males), where β2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction (MVC) of m. quadriceps was measured, followed by exercise to fatigue at 120% of maximal oxygen uptake (V˙O2, max ). A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m. quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45 s sprints. Non-fatigued MVCs were 6 ± 3 and 6 ± 2% higher (P &lt; 0.05) with terbutaline than placebo in EXP1 and EXP2, respectively. Furthermore, peak twitch force was 11 ± 7% higher (P &lt; 0.01) with terbutaline than placebo at non-fatigue. After sprints, MVC declined (P &lt; 0.05) to the same levels with terbutaline as placebo, whereas peak twitch force was lower (P &lt; 0.05) and half-relaxation time was prolonged (P &lt; 0.05) with terbutaline. Rates of SR Ca2+ release and uptake at 400 nm [Ca2+] were 15 ± 5 and 14 ± 5% (P &lt; 0.05) higher, respectively, with terbutaline than placebo at non-fatigue, but declined (P &lt; 0.05) to similar levels at time of fatigue. Na+-K+-ATPase activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in maximum rate of activity (Vmax) at time of fatigue. In conclusion, increased contractile force induced by β2-adrenergic stimulation is associated with enhanced rate of Ca2+ release in humans. While β2-adrenergic stimulation elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps, these effects are blunted when muscles fatigue.

  • 44. Høy, M
    et al.
    Olsen, H L
    Bokvist, K
    Buschard, K
    Barg, S
    Rorsman, P
    Gromada, J
    Tolbutamide stimulates exocytosis of glucagon by inhibition of a mitochondrial-like ATP-sensitive K+ (KATP) conductance in rat pancreatic A-cells.2000In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 527 Pt 1, p. 109-20Article in journal (Refereed)
    Abstract [en]

    1. Capacitance measurements were used to examine the effects of the sulphonylurea tolbutamide on Ca2+-dependent exocytosis in isolated glucagon-secreting rat pancreatic A-cells. 2. When applied extracellularly, tolbutamide stimulated depolarization-evoked exocytosis 4.2-fold without affecting the whole-cell Ca2+ current. The concentration dependence of the stimulatory action was determined by intracellular application through the recording pipette. Tolbutamide produced a concentration-dependent increase in cell capacitance. Half-maximal stimulation was observed at 33 microM and the maximum stimulation corresponded to a 3.4-fold enhancement of exocytosis. 3. The stimulatory action of tolbutamide was dependent on protein kinase C activity. The action of tolbutamide was mimicked by the general K+ channel blockers TEA (10 mM) and quinine (10 microM). A similar stimulation was elicited by 5-hydroxydecanoate (5-HD; 10 microM), an inhibitor of mitochondrial ATP-sensitive K+ (KATP) channels. 4. Tolbutamide-stimulated, but not TEA-induced, exocytosis was antagonized by the K+ channel openers diazoxide, pinacidil and cromakalim. 5. Dissipating the transgranular K+ gradient with nigericin and valinomycin inhibited tolbutamide- and Ca2+-evoked exocytosis. Furthermore, tolbutamide- and Ca2+-induced exocytosis were abolished by the H+ ionophore FCCP or by arresting the vacuolar (V-type) H+-ATPase with bafilomycin A1 or DCCD. Finally, ammonium chloride stimulated exocytosis to a similar extent to that obtained with tolbutamide. 6. We propose that during granular maturation, a granular V-type H+-ATPase pumps H+ into the secretory granule leading to the generation of a pH gradient across the granular membrane and the development of a positive voltage inside the granules. The pumping of H+ is facilitated by the concomitant exit of K+ through granular K+ channels with pharmacological properties similar to those of mitochondrial KATP channels. Release of granules that have been primed is then facilitated by the addition of K+ channel blockers. The resulting increase in membrane potential promotes exocytosis by unknown mechanisms, possibly involving granular alkalinization.

  • 45.
    Islam, Md. Shahidul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    CICR takes centre stage in beta-cells: a cute cascade connects cAMP to CICR2010In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 588, no 24, p. 4853-4853Article in journal (Other academic)
  • 46. Jacobs, Robert A.
    et al.
    Meinild Lundby, Anne-Kristine
    Fenk, Simone
    Gehrig, Saskia
    Christoph, Siebenmann
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology. University of Zürich, Switzerland.
    Flück, Daniela
    Kirk, Niels
    Hilty, Matthias P.
    Lundby, Carsten
    Twenty-eight days of exposure to 3,454 m increases mitochondrial volume density in human skeletal muscle2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 594, no 5, p. 1151-1166Article in journal (Refereed)
    Abstract [en]

    The role of hypoxia on skeletal muscle mitochondria is controversial. Studies superimposing exercise training with hypoxic exposure demonstrate an increase in skeletal muscle mitochondrial volume density (MitoVD ) over equivalent normoxic training. In contrast, a reduction in both skeletal muscle mass and MitoVD have been reported following mountaineering expeditions. These observations may however be confounded by negative energy balance, which may obscure the results. Accordingly we sought to examine the effects of high altitude hypoxic exposure on mitochondrial characteristics, with emphasis on MitoVD , while minimizing changes in energy balance. For this purpose, skeletal muscle biopsies were obtained from 9 lowlanders at sea level (Pre) and following 7 (7 Days) and 28 (28 Days) days of exposure to 3454 m. Maximal ergometer power output, whole-body weight and composition, leg lean mass, and skeletal muscle fibre area all remained unchanged following the altitude exposure. Transmission electron microscopy determined intermyofibrillar (IMF) MitoVD was augmented (P = 0.028) by 11.5 ± 9.2% from Pre (5.05 ± 0.9%) to Day 28 (5.61 ± 0.04%). On the contrary, there was no change in subsarcolemmal (SS) MitoVD . As a result total MitoVD (IMF + SS) was increased (P = 0.031) from 6.20 ± 1.5% at Pre to 6.62 ± 1.4% on Day 28 (7.8 ± 9.3%). At the same time no changes in mass-specific respiratory capacities, mitochondrial protein or antioxidant content were found. This study demonstrates that skeletal muscle MitoVD may increase with 28 days acclimation to 3454 m.

  • 47.
    Jiang, Chonghe
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Maziéres, L
    Lindström, Sivert
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Cold- and menthol-sensitive C afferents of cat urinary bladder2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 543, no 1, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Cold-sensitive C afferents of the urinary bladder were studied in adult anaesthetised with a-chloralose. The bladder was catheterised for fluid instillations and bladder pressure recordings. Pelvic nerve branches were stimulated electrically close to the bladder. Evoked afferent activity was recorded from dissected filaments of the ipsilateral S1-S2 dorsal roots. Responsive afferents were identified using the 'marking technique', based on activity-dependent decrease in C fibre conduction velocity. Of 108 examined bladder C afferents, 14 were activated by innocuous cooling of the bladder wall. Their conduction velocities ranged from 0.6 to 1.7 ms-1 and their activity dependent decrease in conduction velocity was <10%. All nine cold-sensitive afferents tested responded to methol exposure. Cold-sensitive C afferents failed to bladder filling with body-warm saline and to active bladder contractions. These characteristic indicate that the cold-sensitive C afferents of the bladder resemble cutaneous cold receptors rather than cold-sensitive mechanoreceptors or nociceptors. It is concluded that the bladder wall is endowed with cold receptors with unmyelinated C afferents in the pelvic nerves and that these afferents are responsible for bladder cooling reflex.

  • 48. Jorum, E
    et al.
    Lundberg, Lars
    Torebjörk, E
    Peripheral projections of nociceptive unmyelinated axons in the human peroneal nerve1989In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 416, no 1, p. 291-301Article in journal (Refereed)
    Abstract [en]

    1. Previous knowledge of the anatomical course of unmyelinated (C) axons along a peripheral nerve has been scarce and has led to the concept of the axons in a constantly interchanging position. 2. Results obtained by microneurography in the peroneal nerve at knee or ankle levels in awake humans demonstrated that the receptive fields of neighbouring C units in the nerve cluster in close vicinity on the skin of the foot or the ankle. These findings indicate that C afferents run closely together throughout large portions of the peripheral nerve. 3. Intraneural microstimulation performed at neural sites where nociceptive C units were recorded induced painful sensations projected to the skin. When the stimulus intensity was increased, there was typically a concentric increase in the area of projected pain, rather than recruitment of several scattered pain projections. This finding further supports the hypothesis of a neighbouring relation of nociceptive C axons within nerve fascicles, implying spatial recruitment of adjacent axons in the nerve with adjacent peripheral projections. 4. A pain locognosia test performed during ischaemic block of impulse conduction in myelinated fibres demonstrated a fairly precise cerebral localization of noxious events on the foot from the input of C afferent fibres alone.

  • 49.
    Kadi, Fawzi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Schjerling, Peter
    Andersen, Lars L.
    Charifi, Nadia
    Madsen, Jørgen L.
    Christensen, Lasse R.
    Andersen, Jesper L.
    The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 558, no Pt 3, p. 1005-1012Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the modulation of satellite cell content and myonuclear number following 30 and 90 days of resistance training and 3, 10, 30, 60 and 90 days of detraining. Muscle biopsies were obtained from the vastus lateralis of 15 young men (mean age: 24 years; range: 20-32 years). Satellite cells and myonuclei were studied on muscle cross-sections stained with a monoclonal antibody against CD56 and counterstained with Mayer's haematoxylin. Cell cycle markers CyclinD1 and p21 mRNA levels were determined by Northern blotting. Satellite cell content increased by 19% (P= 0.02) at 30 days and by 31% (P= 0.0003) at 90 days of training. Compared to pre-training values, the number of satellite cells remained significantly elevated at 3, 10 and 60 days but not at 90 days of detraining. The two cell cycle markers CyclinD1 and p21 mRNA significantly increased at 30 days of training. At 90 days of training, p21 was still elevated whereas CyclinD1 returned to pre-training values. In the detraining period, p21 and CyclinD1 levels were similar to the pre-training values. There were no significant alterations in the number of myonuclei following the training and the detraining periods. The fibre area controlled by each myonucleus gradually increased throughout the training period and returned to pre-training values during detraining. In conclusion, these results demonstrate the high plasticity of satellite cells in response to training and detraining stimuli and clearly show that moderate changes in the size of skeletal muscle fibres can be achieved without the addition of new myonuclei.

  • 50.
    Kalezic, Ivana
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bugaychenko, Larisa A.
    Department of Movement Physiology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine.
    Kostyukov, Alexander I.
    Department of Movement Physiology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine.
    Pilyavskii, Alexander I.
    Department of Movement Physiology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine.
    Ljubisavljevic, Milos
    Department of Neurophysiology, Institute for Medical Research, Belgrade, Serbia and Montenegro.
    Windhorst, Uwe
    Centre for Musculoskeletal Research, University of Gävle.
    Johansson, Håkan
    Centre for Musculoskeletal Research, University of Gävle.
    Fatigue-related depression of the feline monosynaptic gastrocnemius-soleus reflex2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 556, no 1, p. 293-296Article in journal (Refereed)
    Abstract [en]

    In decerebrate cats, changes in the monosynaptic reflex (MSR) of gastrocnemius-soleus (G-S) motoneurones were studied after fatiguing stimulation (FST) of the G-S muscles. Monosynaptic reflexes were evoked by stimulation of Ia fibres in the G-S nerve and recorded from a filament of ventral root (VR) L7. FST (intermittent 40 s(-1) stimulation for 10-12 min) was applied to the distal part of the cut VR S1. FST reduced MSR amplitudes to 0.64 +/- 0.04 (mean +/-s.e.m.) of the prefatigue values. The suppression remained stable for approximately 25 min and then MSR amplitudes gradually returned towards the normal. To test for the involvement of presynaptic and recurrent inhibition, MSRs were conditioned by stimulation of the nerve to the posterior biceps and semitendinosus (PBSt) muscles or a filament of VR L7, respectively. The intensity of presynaptic inhibition (reduction of the normalized value of MSR amplitude during conditioning) increased from 0.19 +/- 0.02 in prefatigue to 0.44 +/- 0.04 within a 5.3-18.2 min interval after FST, followed by a recovery. In contrast, the intensity of recurrent inhibition first diminished from 0.23 +/- 0.02 in prefatigue to 0.15 +/- 0.01 within 15.6-30.1 min after FST and then gradually recovered. Both primary afferent depolarization and the intensity of antidromic discharges in primary afferents increased with the presynaptic inhibition intensity. These results demonstrate a fatigue-related suppression of Ia excitation of synergistic motoneurones, probably arising from the activation of group III and IV afferents. The effects could in part be due to increased presynaptic inhibition, while recurrent inhibition plays a minor role.

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