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Decrease of a Current Mediated by Kv1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism.
- Source :
-
Cell reports [Cell Rep] 2016 Sep 06; Vol. 16 (10), pp. 2749-2762. Date of Electronic Publication: 2016 Aug 25. - Publication Year :
- 2016
-
Abstract
- The mechanism underlying a hypercholinergic state in Parkinson's disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP 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 Kv1.3-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 KCa channels.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Aging pathology
Animals
Membrane Potentials drug effects
Mice
Oxidopamine
Phenotype
Protein Subunits metabolism
Scorpion Venoms pharmacology
Synapses drug effects
Synapses metabolism
Cholinergic Agents metabolism
Interneurons metabolism
Ion Channel Gating drug effects
Kv1.3 Potassium Channel metabolism
Neostriatum metabolism
Parkinsonian Disorders metabolism
Parkinsonian Disorders physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 27568555
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.08.016