Decrease of a Current Mediated by Kv1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism

Cell Rep. 2016 Sep 6;16(10):2749-2762. doi: 10.1016/j.celrep.2016.08.016. Epub 2016 Aug 25.


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.

MeSH terms

  • Aging / pathology
  • Animals
  • Cholinergic Agents / metabolism*
  • Interneurons / metabolism*
  • Ion Channel Gating* / drug effects
  • Kv1.3 Potassium Channel / metabolism*
  • Membrane Potentials / drug effects
  • Mice
  • Neostriatum / metabolism*
  • Oxidopamine
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / physiopathology*
  • Phenotype
  • Protein Subunits / metabolism
  • Scorpion Venoms / pharmacology
  • Synapses / drug effects
  • Synapses / metabolism


  • Cholinergic Agents
  • Kv1.3 Potassium Channel
  • Protein Subunits
  • Scorpion Venoms
  • margatoxin
  • Oxidopamine