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XB-ART-11198
Epilepsia 2000 Jan 01;41S1:25-9.
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Differential sensitivity of recombinant GABA(A) receptors expressed in Xenopus oocytes to modulation by topiramate.

Gordey M , DeLorey TM , Olsen RW .


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PURPOSE: This study evaluated the modulatory effects of topiramate (TPM) on various subtypes of recombinant rat gamma-aminobutyric acid A (GABA(A)) receptors expressed in Xenopus oocytes. METHODS: Specific subunits of GABA(A) receptors were expressed in Xenopus oocytes. Voltage-clamp recordings of currents were performed after application of TPM (1-100 microM) to these oocytes in the presence or absence of GABA. RESULTS: In a concentration-dependent fashion, TPM (1-100 microM) reversibly inhibited GABA-evoked Cl- currents in oocytes expressing either alpha1beta2gamma2S and alpha2beta2gamma2S recombinant GABA(A) receptors and reduced the current-fading rate in alpha1beta2gamma2S-expressing oocytes. Topiramate was effective at GABA concentrations of 1-10 microM but not at 100 microM. Topiramate (1-100 microM) potentiated GABA-evoked Cl- currents and increased the fading rate in oocytes expressing the alpha6beta2gamma2S GABA(A) receptor. It had no effect on Cl- currents mediated through the alpha4beta2gamma2S receptor or through the mixed population of GABA(A) 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 GABA(A) receptors as assessed by changes in the fading rates of GABA-evoked Cl- currents, possibly by effects on second-messenger systems.

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