Cited by 60Ion channel regulation and functionAnesthesia and Sedative AgentsNicotinic Acetylcholine Receptors Study

Modulation of a voltage-gated Na + channel by sevoflurane involves multiple sites and distinct mechanisms

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Barber, Annika F., Carnevale, Vincenzo, Klein, Michael L., Eckenhoff, Roderic G., Covarrubias, Manuel·2014·Proceedings of the National Academy of Sciences

Abstract

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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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
Published
2014-04-21
Volume
111
Issue
18
Pages
6726-6731
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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