Pregnenolone sulfate and dehydroepiandrosterone sulfate inhibit GABA-gated chloride currents in Xenopus oocytes expressing picrotoxin-insensitive GABA(A) receptors

We examined the effects of picroloxinin, pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS) on γ-aminobutyric acid (GABA) responses in Xenopus oocytes injected with wild type α1, β2 and γ2 GABA(A) receptor subunits and in oocytes injected with wild type α1 and β2 subunits and a mutated γ2 subunit that eliminates picrotoxin sensitivity. All three agents inhibited GABA currents in oocytes injected with wild type subunits. Oocytes injected with the mutated γ2 subunit showed no inhibition of GABA responses by picrotoxinin at concentrations up to 100 μM. PS and DHEAS inhibited GABA currents at similar concentrations in both sets of oocytes. These results indicate that PS and DHEAS do not require a functional picrotoxin site for inhibition of GABA responses.