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 α-bungarotoxin (α-BuTX-ICs) in cultured rat cortical neurons in a fast and reversible manner, as determined by standard whole-cell pa...

Full description

Saved in:
Bibliographic Details
Published in:Molecular pharmacology 1999-01, Vol.55 (1), p.39-49
Main Authors: Aistrup, G L, Marszalec, W, Narahashi, T
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Animals
Bungarotoxins - pharmacology
Cells, Cultured
Ethanol - pharmacology
Female
Frontal Lobe - drug effects
Frontal Lobe - physiology
gamma-Aminobutyric Acid - pharmacology
N-Methylaspartate - pharmacology
Pregnancy
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic - drug effects
Receptors, Nicotinic - physiology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 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.
ISSN:0026-895X
1521-0111
DOI:10.1124/mol.55.1.39