Modulation of a voltage-gated Na + channel by sevoflurane involves multiple sites and distinct mechanisms
Open accessAbstract
Significance: Understanding of the mechanisms of modulation of voltage-gated Na + (Na V ) channels by general anesthetic agents such as sevoflurane is critical to interpret their role in general anesthesia. By using the bacterial Na V channel analogue NaChBac plus a combination of computational and electrophysiological analyses, this work strongly suggests a multisite mechanism of sevoflurane action on Na V channels. Furthermore, computer simulations suggest specific putative anesthetic sites worthy of further investigation.
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Inhibitory actions of anesthetics are conserved in the bacterial sodium channel NaChBac.
“Similar inhibitory actions are also conserved in the smaller, yet homologous bacterial sodium channel, NaChBac [71, 72].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [72]
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Muller, M. P., Jiang, T., Sun, C., Lihan, M., Pant, S., Mahinthichaichan, P., Trifan, A., & Tajkhorshid, E. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00608 · Cited by 282 · see citing works
The Biology of General Anesthesia from Paramecium to Primate
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Pal, D., Jones, J. M., Wisidagamage, S., Meisler, M. H., & Mashour, G. A. (2015) · PLOS ONE · doi:10.1371/journal.pone.0134960 · Cited by 17 · see citing works
- Authors
- Barber, A. F., Carnevale, V., Klein, M. L., Eckenhoff, R. G., & Covarrubias, M.
- Affiliations
- Thomas Jefferson University (US)
- Temple University (US)
- University of Pennsylvania (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-04-21
- Volume
- 111
- Issue
- 18
- Pages
- 6726-6731
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4020080
- OpenAlex
- W2063896182
- Cited by
- 60
- References
- 54
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 8 · 2018: 13 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 3
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- U.S. Public Health Service (NIGMS P-01 55876, NINDS F31 077689)
- National Institute on Alcohol Abuse and Alcoholism (T32AA007463)
- National Institute of General Medical Sciences (P01GM055876)
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- 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
- sevoflurane, voltage-gated sodium channels, NaChBac, general anesthetics, anesthetic binding sites, channel gating kinetics, open channel block, halogenated anesthetics, anesthetic mechanisms
- MeSH terms
- Sevoflurane, Bacterial Proteins, Binding Sites, Humans, Kinetics, Methyl Ethers, Models, Molecular, Protein Conformation, Recombinant Proteins, Sodium Channels, Ion Channel Gating, Patch-Clamp Techniques, Anesthetics, Inhalation, Electrophysiological Phenomena, Molecular Dynamics Simulation, HEK293 Cells
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