Effect of Isoflurane and Other Potent Inhaled Anesthetics on Minimum Alveolar Concentration, Learning, and the Righting Reflex in Mice Engineered to Express α1γ-Aminobutyric Acid Type A Receptors Unresponsive to Isoflurane
Abstract
BACKGROUND: Enhancement of the function of gamma-aminobutyric acid type A receptors containing the alpha1 subunit may underlie a portion of inhaled anesthetic action. To test this, the authors created gene knock-in mice harboring mutations that render the receptors insensitive to isoflurane while preserving sensitivity to halothane. METHODS: The authors recorded miniature inhibitory synaptic currents in hippocampal neurons from hippocampal slices from knock-in and wild-type mice. They also determined the minimum alveolar concentration (MAC), and the concentration at which 50% of animals lost their righting reflexes and which suppressed pavlovian fear conditioning to tone and context in both genotypes. RESULTS: Miniature inhibitory postsynaptic currents decayed more rapidly in interneurons and CA1 pyramidal cells from the knock-in mice compared with wild-type animals. Isoflurane (0.5-1 MAC) prolonged the decay phase of miniature inhibitory postsynaptic currents in neurons of the wild-type mice, but this effect was significantly reduced in neurons from knock-in mice. Halothane (1 MAC) slowed the decay of miniature inhibitory postsynaptic current in both genotypes. The homozygous knock-in mice were more resistant than wild-type controls to loss of righting reflexes induced by isoflurane and enflurane, but not to halothane. The MAC for isoflurane, desflurane, and halothane did not differ between knock-in and wild-type mice. The knock-in mice and wild-type mice did not differ in their sensitivity to isoflurane for fear conditioning. CONCLUSIONS: gamma-Aminobutyric acid type A receptors containing the alpha1 subunit participate in the inhibition of the righting reflexes by isoflurane and enflurane. They are not, however, involved in the amnestic effect of isoflurane or immobilizing actions of inhaled agents.
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Binding to GABA receptors does appear to contribute to unconsciousness caused by isoflurane because mice with nonfunctional GABARs are somewhat resistant to isoflurane.
“For example, binding to GABA receptors does appear to contribute to unconsciousness caused by isoflurane because mice with nonfunctional GABARs are somewhat resistant to isoflurane (Sonner et al. 2007).”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Sonner et al. 2007
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Self-citation
- Authors
- Sonner, J. M., Werner, D. F., Elsen, F. P., Xing, Y., Liao, M., Harris, R. A., Harrison, N. L., Fanselow, M. S., Eger, E. I., & Homanics, G. E.
- Affiliations
- Associate Professor of Anesthesia and Perioperative Care.
- Graduate Student.
- Postdoctoral Fellow.
- Research Assistant.
- The University of Texas at Austin (US)
- Cornell University (US)
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- University of Pittsburgh (US)
- ORCID
- Venue
- Anesthesiology
- Published
- 2007-01-01
- Volume
- 106
- Issue
- 1
- Pages
- 107-113
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W2132817240
- Cited by
- 82
- References
- 0
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 7
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (T32 MH18273, T32MH018273)
- National Institute of General Medical Sciences (P01GM047818, GM 47818)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- isoflurane, GABAA receptor, alpha1 subunit, inhalational anesthetics, minimum alveolar concentration, righting reflex, halothane, enflurane, desflurane, miniature inhibitory postsynaptic currents, hippocampal interneurons, CA1 pyramidal neurons, fear conditioning
- MeSH terms
- Animals, Female, Hippocampus, Isoflurane, Learning, Male, Motor Activity, Mutation, Pulmonary Alveoli, Receptors, GABA-A, Reflex, Anesthetics, Inhalation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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