The anticonvulsant retigabine is a subtype selective modulator of GABAA receptors

Epilepsia
Marco TrevenHelmut Kubista

Abstract

Within its range of therapeutic plasma concentrations, the anticonvulsant retigabine (ezogabine) is believed to selectively act on Kv7 channels. Here, the contribution of specific γ-aminobutyric acid (GABA)A receptor subtypes to the antiseizure effects of retigabine was investigated. Using patch-clamp recordings, seizure-like activity, tonic currents, and GABA-induced currents in hippocampal neurons were tested for their sensitivity toward retigabine, as were recombinant GABAA receptors expressed in tsA 201 cells. Retigabine reduced seizure-like activity elicited by low Mg(2+) in a concentration-dependent manner with half maximal inhibition at 1 μm. Seizure-like activity triggered by blocking either Kv7 channels or GABAA receptors was equally reduced by retigabine, but when these channels/receptors were blocked simultaneously, the inhibition was lost. Retigabine (10 μm) enhanced bicuculline-sensitive tonic currents in hippocampal neurons, but failed to affect GABA-evoked currents. However, when receptors involved in phasic GABAergic inhibition were blocked by penicillin, retigabine did enhance GABA-evoked currents. In tsA 201 cells expressing various combinations of GABAA receptor subunits, 10 μm retigabine enhanced currents th...Continue Reading

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Methods Mentioned

BETA
pharmacotherapy
transfection

Software Mentioned

GraphPad Prism

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