Decrease of a current mediated by Kv1.3 channels causes striatal cholinergic interneuron hyperexcitability in experimental parkinsonism

IRENE TARAVINI; ALEJANDRA PROST; LORENA RELA; IRENE TARAVINI; ALEJANDRA PROST; LORENA RELA; EDEN FLORES-BARRERA; MARÍA ELENA AVALE; MARIO GUSTAVO MURER; EDEN FLORES-BARRERA; CECILIA TUBERT; MARÍA ELENA AVALE; GONZALO SANCHEZ; MARIO GUSTAVO MURER; KUEI Y. TSENG; CECILIA TUBERT; GONZALO SANCHEZ; KUEI Y. TSENG

Cell Reports

SPRINGER

Lugar: Cambridge, MA; Año: 2016 vol. 16 p. 2749 - 2762

The mechanism underlying a ?hypercholinergic state? in Parkinson?s disease (PD) remains uncertain. Here we found that a disruption of 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 interneurons 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. Together, 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.