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Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-8493-0114
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
University of Copenhagen, Denmark.
University of Copenhagen, Denmark.
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2016 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 218, no 1, p. 28-37Article in journal (Refereed) Published
Abstract [en]

Aim: Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage-gated sodium and calcium channels. Effects on neuronal potassium channels are less explored and experimental data ambiguous. The aim of this study was to investigate anti-excitable effects of polyunsaturated fatty acids on the neuronal M-channel, important for setting the resting membrane potential in hippocampal and dorsal root ganglion neurones. Methods: Effects of fatty acids and fatty acid analogues on mouse dorsal root ganglion neurones and on the human KV7.2/3 channel expressed in Xenopus laevis oocytes were studied using electrophysiology. Results: Extracellular application of physiologically relevant concentrations of the polyunsaturated fatty acid docosahexaenoic acid hyperpolarized the resting membrane potential (-2.4 mV by 30 mu M) and increased the threshold current to evoke action potentials in dorsal root ganglion neurones. The polyunsaturated fatty acids docosahexaenoic acid, alpha-linolenic acid and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV7.2/3 channel expressed in Xenopus oocytes, by shifting the conductance-vs.-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 mu M). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV7.2/3 channel. Conclusions: These findings suggest that circulating polyunsaturated fatty acids, with a minimum requirement of multiple double bonds and a charged carboxyl group, dampen excitability by opening neuronal M-channels. Collectively, our data bring light to the molecular targets of polyunsaturated fatty acids and thus a possible mechanism by which polyunsaturated fatty acids reduce neuronal excitability.

Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 218, no 1, p. 28-37
Keywords [en]
electrophysiology; epilepsy; excitability; KCNQ potassium channel family; M-channel; polyunsaturated fatty acids
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-133537DOI: 10.1111/apha.12663ISI: 000383579300006PubMedID: 26914447OAI: oai:DiVA.org:liu-133537DiVA, id: diva2:1060860
Note

Funding Agencies|Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Brain Foundation; County Council of Ostergotland; Queen Silvias Anniversary Foundation

Available from: 2016-12-30 Created: 2016-12-29 Last updated: 2018-01-25

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