Publikationsdatenbank

Lower KV7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia (2016)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Sander, Svenja E (WE 14)

Diwan, Mustansir

Raymond, Roger

Nobrega, José N

Richter, Angelika

Quelle

CNS & neurological disorders drug targets

Bandzählung: 15

Heftzählung: 1

Seiten: 95 – 101

ISSN: 1996-3181

Sprache

Englisch

Verweise

Pubmed: 26553166

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Dystonia is a hyperkinetic disabling movement disorder. In the dt(sz) hamster, a model of paroxysmal dystonia, pronounced antidystonic effects of the KV7.2-5 potassium channel opener retigabine and aggravation of dystonia by a selective KV7.2-5 blocker indicated a pathophysiological role of an abnormal expression of KV7 channels. We therefore investigated the expression of KV7 subunits in brains of dystonic hamsters. While KV7.2 and KV7.3 subunits were unaltered, lower KV7.5 mRNA levels became evident in motor areas and in limbic structures of dystonic hamsters. The KV7.2/3 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 KV7.5 channels. The experiments indicate a functional relevance for KV7.5 channels in paroxysmal dystonia. We suggest that compounds highly selective for subtypes of KV7 channels, i.e. for KV7.5, may provide new therapeutic approaches.