Guanosine phosphate analogs modulate ethanol potentiation of GABAA-mediated synaptic currents in hippocampal CA1 neurons

Recent studies have demonstrated that ethanol potentiation of GABA_A receptor function can be regulated by second-messenger-dependent processes. As a preliminary step to further characterize this interaction, we used the whole-cell patch-clamp technique to study the effects of guanosine phosphate analogs on ethanol potentiation of GABA_A-mediated synaptic transmission, in rat hippocampal CA1 neurons. Intracellular dialysis with 400 μM GDPβS, an analog that inhibits G-protein coupled events, significantly reduced ethanol, but not pentobarbital, potentiation of IPSCs. In contrast, dialysing neurons with 100 μM GTPγS, an irreversible G-protein activator, selectively facilitated ethanol potentiation of GABA_A IPSCs. These results suggest that one or more G-protein coupled events regulate the ethanol sensitivity of synaptic GABA_A receptors.