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Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 neurons: possible role of protein kinase C.
J Pharmacol Exp Ther. 1994 Mar; 268(3):1388-95.JP

Abstract

Ethanol has been reported to interact with numerous voltage- and ligand-gated ion channels in central mammalian neurons. In particular, the type A gamma-aminobutyric acid (GABAA) receptor/chloride ionophore complex has received considerable attention as a cellular substrate for ethanol and other sedative-hypnotic drugs. Direct electrophysiological evidence that ethanol modulates GABAA receptor function has been controversial. In this study, we investigated the effects of ethanol on the GABAA receptors that mediate fast inhibitory synaptic transmission in the rat hippocampus. Using the whole-cell patch-clamp recording technique in brain slices, we found that clinically relevant concentrations of ethanol (10-50 mM) potentiate pharmacologically isolated GABAA-mediated inhibitory postsynaptic currents (IPSCs) recorded from rat hippocampal CA1 neurons. In addition, we demonstrate that ethanol- but not diazepam-mediated enhancement of GABAA IPSCs requires intracellular ATP and can be blocked by Ro-31-8220 or PKC19-31, specific inhibitors of protein kinase C. Furthermore, the active phorbol ester 4-beta-PDBu but not its inactive analog also interferes with ethanol enhancement of GABAA IPSCs. These results demonstrate that ethanol potentiation of pharmacologically isolated GABAA IPSCs can be modulated by protein kinase C.

Authors+Show Affiliations

Playfair Neuroscience Unit, Toronto Hospital Research Institute, Ontario, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8138953

Citation

Weiner, J L., et al. "Potentiation of GABAA-mediated Synaptic Current By Ethanol in Hippocampal CA1 Neurons: Possible Role of Protein Kinase C." The Journal of Pharmacology and Experimental Therapeutics, vol. 268, no. 3, 1994, pp. 1388-95.
Weiner JL, Zhang L, Carlen PL. Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 neurons: possible role of protein kinase C. J Pharmacol Exp Ther. 1994;268(3):1388-95.
Weiner, J. L., Zhang, L., & Carlen, P. L. (1994). Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 neurons: possible role of protein kinase C. The Journal of Pharmacology and Experimental Therapeutics, 268(3), 1388-95.
Weiner JL, Zhang L, Carlen PL. Potentiation of GABAA-mediated Synaptic Current By Ethanol in Hippocampal CA1 Neurons: Possible Role of Protein Kinase C. J Pharmacol Exp Ther. 1994;268(3):1388-95. PubMed PMID: 8138953.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 neurons: possible role of protein kinase C. AU - Weiner,J L, AU - Zhang,L, AU - Carlen,P L, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 1388 EP - 95 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 268 IS - 3 N2 - Ethanol has been reported to interact with numerous voltage- and ligand-gated ion channels in central mammalian neurons. In particular, the type A gamma-aminobutyric acid (GABAA) receptor/chloride ionophore complex has received considerable attention as a cellular substrate for ethanol and other sedative-hypnotic drugs. Direct electrophysiological evidence that ethanol modulates GABAA receptor function has been controversial. In this study, we investigated the effects of ethanol on the GABAA receptors that mediate fast inhibitory synaptic transmission in the rat hippocampus. Using the whole-cell patch-clamp recording technique in brain slices, we found that clinically relevant concentrations of ethanol (10-50 mM) potentiate pharmacologically isolated GABAA-mediated inhibitory postsynaptic currents (IPSCs) recorded from rat hippocampal CA1 neurons. In addition, we demonstrate that ethanol- but not diazepam-mediated enhancement of GABAA IPSCs requires intracellular ATP and can be blocked by Ro-31-8220 or PKC19-31, specific inhibitors of protein kinase C. Furthermore, the active phorbol ester 4-beta-PDBu but not its inactive analog also interferes with ethanol enhancement of GABAA IPSCs. These results demonstrate that ethanol potentiation of pharmacologically isolated GABAA IPSCs can be modulated by protein kinase C. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8138953/Potentiation_of_GABAA_mediated_synaptic_current_by_ethanol_in_hippocampal_CA1_neurons:_possible_role_of_protein_kinase_C_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8138953 DB - PRIME DP - Unbound Medicine ER -