RT Journal Article
SR Electronic
T1 Ethanol Modulation of Nicotinic Acetylcholine Receptor Currents in Cultured Cortical Neurons
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 39
OP 49
DO 10.1124/mol.55.1.39
VO 55
IS 1
A1 Gary L. Aistrup
A1 William Marszalec
A1 Toshio Narahashi
YR 1999
UL http://molpharm.aspetjournals.org/content/55/1/39.abstract
AB Ethanol, at physiologically relevant concentrations, significantly enhanced high-affinity neuronal nicotinic acetylcholine receptor (NnAChR) currents insensitive to α-bungarotoxin (α-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 μM ACh. No plateau for this ethanol-induced enhancement of α-BuTX-ICs was reached. The maximal α-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 α-BuTX (α-BuTX-SCs) (5 ± 4% to 29 ± 6% inhibition by 10 to 300 mM ethanol at 300 to 1000 μM ACh). This neuronal preparation also enabled comparison of ethanol action on NnAChRs with its action on N-methyl-d-aspartate receptor currents and γ-aminobutyric acid receptor currents within the same neurons. Ethanol (100 mM) was more potent at enhancing NnAChR α-BuTX-ICs (61 ± 9% enhancement) than it was at enhancing γ-aminobutyric acid receptor current (3 ± 3% enhancement—not statistically significant) or at inhibitingN-methyl-d-aspartate receptor currents (∼35 ± 7% inhibition). Thus, NnAChRs, particularly those insensitive to α-BuTX, may be sensitive conduits through which ethanol can mediate some of its actions in the brain.