Cited by 319Anesthesia and Sedative AgentsNeuroscience and Neuropharmacology ResearchAnesthesia and Neurotoxicity Research

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Sedation and Anesthesia Mediated by Distinct GABA A Receptor Isoforms

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Reynolds, David S., Rosahl, Thomas W., Cirone, Jennifer, O'Meara, Gillian F., Haythornthwaite, Alison, Newman, Richard J., Myers, Janice, Sur, Cyrille, Howell, Owain, Rutter, A. Richard, Atack, John, Macaulay, Alison J., Hadingham, Karen L., Hutson, Peter H., Belelli, Delia, Lambert, Jeremy J., Dawson, Gerard R., McKernan, Ruth, Whiting, Paul J., Wafford, Keith A.·2003·The Journal of Neuroscience

DOI 10.1523/jneurosci.23-24-08608.2003PMC PMC6740367

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Abstract

The specific mechanisms underlying general anesthesia are primarily unknown. The intravenous general anesthetic etomidate acts by potentiating GABA A receptors, with selectivity for β2 and β3 subunit-containing receptors determined by a single asparagine residue. We generated a genetically modified mouse containing an etomidate-insensitive β2 subunit (β2 N265S) to determine the role of β2 and β3 subunits in etomidate-induced anesthesia. Loss of pedal withdrawal reflex and burst suppression in the electroencephalogram were still observed in the mutant mouse, indicating that loss of consciousness can be mediated purely through β3-containing receptors. The sedation produced by subanesthetic doses of etomidate and during recovery from anesthesia was present only in wild-type mice, indicating that the β2 subunit mediates the sedative properties of anesthetics. These findings show that anesthesia and sedation are mediated by distinct GABA A receptor subtypes.

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Authors: Reynolds, D. S., Rosahl, T. W., Cirone, J., O'Meara, G. F., Haythornthwaite, A., Newman, R. J., Myers, J., Sur, C., Howell, O., Rutter, A. R., Atack, J., Macaulay, A. J., Hadingham, K. L., Hutson, P. H., Belelli, D., Lambert, J. J., Dawson, G. R., McKernan, R., Whiting, P. J., & Wafford, K. A.
Affiliations: University of Dundee (GB)
ORCID: Rosahl, Thomas W.
Cirone, Jennifer
Howell, Owain
Rutter, A. Richard
Atack, John
Belelli, Delia
Lambert, Jeremy J.
Dawson, Gerard R.
Whiting, Paul J.
Wafford, Keith A.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2003-09-17
Volume: 23
Issue: 24
Pages: 8608-8617
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.23-24-08608.2003
PMC: PMC6740367
OpenAlex: W2140230931
Cited by: 318
References: 35
Citations by year: 2026: 7 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 11 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 14 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 6
FWCI: 32.69
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
PubMed
Funders: Directorate for Biological Sciences
Medical Research Council
Topics: Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords: GABAA receptor, etomidate, general anesthesia, sedation, beta2 subunit, beta3 subunit, loss of consciousness, burst suppression, anesthesia recovery
MeSH terms: Anesthetics, Animals, Anticonvulsants, Behavior, Animal, Binding, Competitive, Cell Separation, Consciousness, Dose-Response Relationship, Drug, Electroencephalography, Etomidate, Hypnotics and Sedatives, Male, Mice, Mutant Strains, Motor Activity, Purkinje Cells, Receptors, GABA-A, Triazoles, Gene Targeting, Patch-Clamp Techniques, Bridged Bicyclo Compounds, Heterocyclic, Protein Isoforms, Recovery of Function, Mice, In Vitro Techniques

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Sedation and Anesthesia Mediated by Distinct GABA A Receptor Isoforms

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