α-Substituted thiobutyrolactones potentiate GABA currents in voltage-clamped chick spinal cord neurons

The effect of the experimental anticonvulsant, α-ethyl,methyl thiobutyrolactone (α-EMTBL), on γ-aminobutyric acid (GABA) currents was examined in cultured chick spinal cord neurons using gigaseal recording techniques. α-EMTBL potentiated GABA responses in a dose-dependent fashion with half-maximal effect at 7 μM. α-EMTBL also augmented the response to maximal doses of GABA. In competition experiments, α-EMTBL relieved the block of GABA currents produced by saturating concentrations of picrotoxinin whereas diazepam and phenobarbital did not. At a single channel level, α-EMTBL increased the probability of opening GABA channels without significantly altering the mean channel open time or the single channel conductance. These results indicate that α-EMTBL potentiates GABA responses and has properties which distinguish it from benzodiazepines or barbiturates.