Dystonia is a hyperkinetic disabling movement disorder. In the dtsz 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.
Keywords: animal model, dyskinesia, dystonia, ICA 27243, KCNQ, voltage-gated potassium channels.
promotion: free to download
Rights & PermissionsPrintExport