Cited by 1,219Neuroscience and Neuropharmacology ResearchAnesthesia and Sedative AgentsNicotinic Acetylcholine Receptors Study

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Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors

Mihic, S. John, Ye, Qing, Wick, Marilee J., Koltchine, Vladimir V., Krasowski, Matthew D., Finn, Suzanne E., Mascia, Maria Paola, Valenzuela, C. Fernando, Hanson, Kirsten K., Greenblatt, Eric P., Harris, R. Adron, Harrison, Neil L.·1997·Nature

DOI 10.1038/38738

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Abstract

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.

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Authors: Mihic, S. J., Ye, Q., Wick, M. J., Koltchine, V. V., Krasowski, M. D., Finn, S. E., Mascia, M. P., Valenzuela, C. F., Hanson, K. K., Greenblatt, E. P., Harris, R. A., & Harrison, N. L.
Affiliations: Atrium Health Wake Forest Baptist (US)
University of Chicago (US)
Denver VA Medical Center (US)
University of Colorado Denver (US)
University of Pennsylvania (US)
Corresponding author: Harrison, Neil L.
ORCID: Mihic, S. John
Krasowski, Matthew D.
Mascia, Maria Paola
Valenzuela, C. Fernando
Hanson, Kirsten K.
Harris, R. Adron
Harrison, Neil L.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1997-09
Volume: 389
Issue: 6649
Pages: 385-389
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/38738
OpenAlex: W1668093331
Cited by: 1,219
References: 27
Citations by year: 2026: 3 · 2025: 9 · 2024: 13 · 2023: 7 · 2022: 11 · 2021: 18 · 2020: 23 · 2019: 21 · 2018: 20 · 2017: 33 · 2016: 34 · 2015: 30 · 2014: 45 · 2013: 50 · 2012: 52
FWCI: 25.86
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords: volatile anesthetics, alcohol, GABAA receptor, glycine receptor, allosteric modulation, transmembrane domain, inhibitory neurotransmitter receptors, ion channels
MeSH terms: Alanine, Ethanol, Amino Acid Sequence, Animals, Binding Sites, Cell Line, Electrophysiology, Enflurane, Glycine, Humans, Molecular Sequence Data, Receptors, GABA-A, Recombinant Fusion Proteins, Serine, Tryptophan, Xenopus, Propofol, Mutagenesis, Sequence Homology, Amino Acid, Receptors, Glycine, Anesthetics, Inhalation, Anesthetics, Intravenous

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