Abstract
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.
Footnotes
- Received July 2, 1998.
- Accepted September 24, 1998.
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Send reprint requests to: Dr. Toshio Narahashi, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611-3008. E-mail: tna597{at}nwu.edu
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This work was supported by National Institutes of Health Grants R01 AA07836, R01 NS14144, and F32 AA05447.
- The American Society for Pharmacology and Experimental Therapeutics
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