Differential sensitivity of recombinant GABA(A) receptors expressed in Xenopus oocytes to modulation by topiramate

Purpose: This study evaluated the modulatory effects of topiramate (TPM) on various subtypes of recombinant rat gamma-aminobutyric acid A (GABA(A)) re ceptors expressed in Xenopus oocytes. Methods: Specific subunits of GABA(A) receptors were expressed in Xenopus o ocytes. Voltage-clamp recordings of currents were performed after applicati on of TPM (1-100 mu M) to these oocytes in the presence or absence of GABA. Results: In a concentration-dependent fashion, TPM (1-100 mu M) reversibly inhibited GABA-evoked Cl- currents in oocytes expressing either alpha(1)bet a(2)gamma(2)S and alpha(2)beta(2)gamma(2)S recombinant GABA(A) receptors an d reduced the current-fading rate in alpha(1)beta(2)gamma(2)S-expressing oo cytes. Topiramate was effective at GABA concentrations of 1-10 mu M but not at 100 mu M. Topiramate (1-100 mu M) potentiated GABA-evoked Cl- currents and increased the fading rate in oocytes expressing the alpha(6)beta(2)gamm a(2)S GABA(A) receptor. It had no effect on Cl- currents mediated through t he alpha(4)beta(2)gamma(2)S receptor or through the mixed population of GAB A(A) receptors expressed from rat brain mRNA. In general, the observed effe cts of TPM were more pronounced on fading rates than on peak Cl- currents. Conclusions: These results indicate that TPM may affect desensitization of GABA(A) receptors as assessed by changes in the fading rates of GABA-evoked Cl- currents, possibly by effects on second-messenger systems.