Guanosine phosphate analogs modulate ethanol potentiation of GABAA-mediated synaptic currents in hippocampal CA1 neurons.
Recent studies have demonstrated that ethanol potentiation of GABAA 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 GABAA-mediated synaptic transmission in rat hippocampal CA1 neurons. Intracellular dialysis with 400 microM GDP beta S, an analog that inhibits G-protein coupled events, significantly reduced ethanol, but not pentobarbital, potentiation of IPSCs. In contrast, dialysing neurons with 100 microM GTP gamma S, an irreversible G-protein activator, selectively facilitated ethanol potentiation of GABAA IPSCs. These results suggest that one or more G-protein coupled events regulate the ethanol sensitivity of synaptic GABAA receptors.
Weiner
J L
JL
Department of Pharmacology, University of Toronto, Ont., Canada.
Zhang
L
L
Carlen
P L
PL
D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000145:classification / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D018756:GABA Antagonists; D006150:Guanine Nucleotides; D018079:Receptors, GABA; C034883:guanosine 5'-O-(2-thiotriphosphate); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000431:Ethanol