Combining endocannabinoids with retigabine for enhanced M-channel effect and improved KV7 subtype selectivity.

ABSTRACT: Retigabine is unique among anticonvulsant drugs by targeting the neuronal M-channel, which is composed of KV7.2/KV7.3 and contributes to the negative neuronal resting membrane potential. Unfortunately, retigabine causes adverse effects, which limits its clinical use. Adverse effects may be reduced by developing M-channel activators with improved KV7 subtype selectivity. The aim of this study was to evaluate the prospect of endocannabinoids as M-channel activators, either in isolation or combined with retigabine. Human KV7 channels were expressed in Xenopus laevis oocytes. The effect of extracellular application of compounds with different properties was studied using two-electrode voltage clamp electrophysiology. Site-directed mutagenesis was used to construct channels with mutated residue

SUBMITTER: Larsson JE 

PROVIDER: S-EPMC7398146 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature