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

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

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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Metadata

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
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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