Elsevier

Brain Research

Volume 665, Issue 2, 5 December 1994, Pages 307-310
Brain Research

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

https://doi.org/10.1016/0006-8993(94)91352-8Get rights and content

Abstract

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 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 GABAA IPSCs. These results suggest that one or more G-protein coupled events regulate the ethanol sensitivity of synaptic GABAA receptors.

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    This work was supported by research grants to P.L.C. from the Medical Research Council (MRC) of Canada and the Alcoholic Beverages Medical Research Foundation.

    **

    We thank Mr. Frank Vidic for his excellent assistance with electronics and computerized data-processing and Taufik Ali Valiante for producing the TCRUNCH software for data analysis. We also thank Patricia L. Watson for helpful discussion.

    L.Z. is supported by the Bloorview Epilepsy Research Program.

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