Differential sensitivity of recombinant GABAA receptors expressed in xenopus oocytes to modulation by topiramate

Abstract

Purpose: This study evaluated the modulatory effects of topiramate (TPM) on various subtypes of recombinant rat γ-aminobutyric acid A (GABAA) receptors expressed in Xenopus oocytes. Methods: Specific subunits of GABAA receptors were expressed in Xenopus oocytes. Voltage-clamp recordings of currents were performed after application of TPM (1-100 μM) to these oocytes in the presence or absence of GABA. Results: In a concentration-dependent fashion, TPM (1-100 μM) reversibly inhibited GABA-evoked Cl- currents in oo-cytes expressing either α1β2γ2S and α2β2γ2S recombinant GABAA receptors and reduced the current-fading rate in α1β2γ2S-expressing oocytes. Topiramate was effective at GABA concentrations of 1-10 μM but not at 100 μM. Topiramate (1-100 μM) potentiated GABA-evoked Cl- currents and increased the fading rate in oocytes expressing the α6β2γ2S GABAA receptor. It had no effect on Cl- currents mediated through the α4β2γ2S receptor or through the mixed population of GABAA receptors expressed from rat brain mRNA. In general, the observed effects of TPM were more pronounced on fading rates than on peak Cl- currents. Conclusions: These results indicate that TPM may affect desensitization of GABAA receptors as assessed by changes in the fading rates of GABA-evoked Cl- currents, possibly by effects on second-messenger systems. © International League Against Epilepsy.