Ethanol modulation of nicotinic acetylcho1ine receptor currents in cultured cortical neurons

Gary L. Aistrup, William Marszalec, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

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. ↓ ± 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-SOs) (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 inhibiting N- 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.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalMolecular pharmacology
Volume55
Issue number1
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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