Lower K_V7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia

Title:Lower K_V7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia

Volume: 15 Issue: 1

Author(s): Svenja E. Sander, Mustansir Diwan, Roger Raymond, José N Nobrega and Angelika Richter

Affiliation:

Keywords: animal model, dyskinesia, dystonia, ICA 27243, KCNQ, voltage-gated potassium channels.

Abstract: Dystonia is a hyperkinetic disabling movement disorder. In the dt^sz hamster, a model of paroxysmal dystonia, pronounced antidystonic effects of the K_V7.2-5 potassium channel opener retigabine and aggravation of dystonia by a selective K_V7.2-5 blocker indicated a pathophysiological role of an abnormal expression of K_V7 channels. We therefore investigated the expression of K_V7 subunits in brains of dystonic hamsters. While K_V7.2 and K_V7.3 subunits were unaltered, lower K_V7.5 mRNA levels became evident in motor areas and in limbic structures of dystonic hamsters. The K_V7.2/3 subunit-preferring channel opener N-(6-chloropyridin-3-yl)-3,4- difluorobenzamide (ICA 27243; 10-30 mg/kg i.p.) failed to reduce the severity of dystonia in mutant hamsters, suggesting that the previously observed antidystonic action of retigabine is mediated by the activation of K_V7.5 channels. The experiments indicate a functional relevance for KV7.5 channels in paroxysmal dystonia. We suggest that compounds highly selective for subtypes of K_V7 channels, i.e. for K_V7.5, may provide new therapeutic approaches.

Cite this article as:

Sander E. Svenja, Diwan Mustansir, Raymond Roger, Nobrega N José and Richter Angelika, Lower K_V7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia, CNS & Neurological Disorders - Drug Targets 2016; 15 (1) . https://dx.doi.org/10.2174/1871527315666151110124136