Ethanol modulation of nicotinic acetylcholine receptor currents in cultured cortical neurons.
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.
Aistrup
G L
GL
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.
Marszalec
W
W
Narahashi
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D000109:Acetylcholine