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Decrease of a Current Mediated by K(v)1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
University of Buenos Aires, Argentina.
University of Entre Rios, Argentina.
Rosalind Franklin University, IL 60064 USA.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. University of Buenos Aires, Argentina.
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2016 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, no 10, 2749-2762 p.Article in journal (Refereed) Published
Abstract [en]

The mechanism underlying a hypercholinergic state in Parkinsons disease (PD) remains uncertain. Here, we show that disruption of the K(v)1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing K(v)1.3 subunits contribute significantly to the orphan potassium current known as I-sAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by K(v)1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on K-Ca channels.

Place, publisher, year, edition, pages
CELL PRESS , 2016. Vol. 16, no 10, 2749-2762 p.
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URN: urn:nbn:se:liu:diva-132057DOI: 10.1016/j.celrep.2016.08.016ISI: 000383880400018PubMedID: 27568555OAI: diva2:1038457

Funding Agencies|Fondo para la Investigacion Cientifica y Tecnologica (FONCYT; Proyecto de Investigacion Cientifica y Tecnologica [PICT]) [2011-521, 2013-1523, 2015-3687]; Tourette Syndrome Association; Universidad de Buenos Aires [UBA-CYT2014-249]

Available from: 2016-10-18 Created: 2016-10-17 Last updated: 2016-11-11

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