Author(s): Aistrup GL, Marszalec W, Narahashi T
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Abstract Ethanol, at physiologically relevant concentrations, significantly enhanced high-affinity neuronal nicotinic acetylcholine receptor (NnAChR) currents insensitive to alpha-bungarotoxin (alpha-BuTX-ICs) in cultured rat cortical neurons in a fast and reversible manner, as determined by standard whole-cell patch-clamp recording techniques. The enhancement was (mean +/- S.D.) 7.7 +/- 5\% to 192 +/- 52\% upon coapplication of 3 to 300 mM ethanol with 1 to 3 microM ACh. No plateau for this ethanol-induced enhancement of alpha-BuTX-ICs was reached. The maximal alpha-BuTX-IC evoked by very high concentrations of ACh also was increased upon coapplication of ethanol. In contrast, ethanol weakly inhibited low-affinity NnAChR currents sensitive to alpha-BuTX (alpha-BuTX-SCs) (5 +/- 4\% to 29 +/- 6\% inhibition by 10 to 300 mM ethanol at 300 to 1000 microM ACh). This neuronal preparation also enabled comparison of ethanol action on NnAChRs with its action on N-methyl-D-aspartate receptor currents and gamma-aminobutyric acid receptor currents within the same neurons. Ethanol (100 mM) was more potent at enhancing NnAChR alpha-BuTX-ICs (61 +/- 9\% enhancement) than it was at enhancing gamma-aminobutyric acid receptor current (3 +/- 3\% enhancement-not statistically significant) or at inhibiting N-methyl-D-aspartate receptor currents (approximately 35 +/- 7\% inhibition). Thus, NnAChRs, particularly those insensitive to alpha-BuTX, may be sensitive conduits through which ethanol can mediate some of its actions in the brain.
This article was published in Mol Pharmacol
and referenced in Biochemistry & Pharmacology: Open Access