ArticleProceedings of the National Academy of Sciences of the United States of America2014
Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Volatile anaesthetics modulate voltage-gated sodium channel function at a site directly linked to channel gating.Nature communications · 2026Article
- Age-dependent electroencephalogram alterations under remimazolam anesthesia.Korean journal of anesthesiology · 2026Observational
- Sevoflurane Inhibits Layer 5 Pyramidal Neurons via Kv1.2-Dependent Modulation of Subthreshold Currents.Journal of neurochemistry · 2026Article
- Chasing allosteric inhibition of the SARS-CoV-2 PLpro via molecular dynamics simulations with flooding fragments (MDFFr).Journal of computer-aided molecular design · 2025Article
- Sevoflurane inhibition of the developmentally expressed neuronal sodium channel NaScientific reports · 2025Article
- Drugs exhibit diverse binding modes and access routes in the Nav1.5 cardiac sodium channel pore.The Journal of general physiology · 2025Article
- A new polymodal gating model of the proton-activated chloride channel.PLoS biology · 2023Article
- Characterizing fenestration size in sodium channel subtypes and their accessibility to inhibitors.Biophysical journal · 2022Article
- Identifying c-fos Expression as a Strategy to Investigate the Actions of General Anesthetics on the Central Nervous System.Current neuropharmacology · 2022Review
- Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.Frontiers in pharmacology · 2022Review
- Binding Sites and the Mechanism of Action of Propofol and a Photoreactive Analogue in Prokaryotic Voltage-Gated Sodium Channels.ACS chemical neuroscience · 2021Article
- Regulation and drug modulation of a voltage-gated sodium channel: Pivotal role of the S4-S5 linker in activation and slow inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Polyamine blockade and binding energetics in the MthK potassium channel.The Journal of general physiology · 2020Article
- Hydrophobic Drug/Toxin Binding Sites in Voltage-Dependent KFrontiers in pharmacology · 2020Review
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol.Frontiers in cellular neuroscience · 2020Article
- The Biology of General Anesthesia from Paramecium to Primate.Current biology : CB · 2019Review
- Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
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5 authors.
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Abstract
Halogenated inhaled general anesthetic agents modulate voltage-gated ion channels, but the underlying molecular mechanisms are not understood. Many general anesthetic agents regulate voltage-gated Na(+) (NaV) channels, including the commonly used drug sevoflurane. Here, we investigated the putative binding sites and molecular mechanisms of sevoflurane action on the bacterial NaV channel NaChBac by using a combination of molecular dynamics simulation, electrophysiology, and kinetic analysis. Structural modeling revealed multiple sevoflurane interaction sites possibly associated with NaChBac modulation. Electrophysiologically, sevoflurane favors activation and inactivation at low concentrations (0.2 mM), and additionally accelerates current decay at high concentrations (2 mM). Explaining these observations, kinetic modeling suggests concurrent destabilization of closed states and low-affinity open channel block. We propose that the multiple effects of sevoflurane on NaChBac result from simultaneous interactions at multiple sites with distinct affinities. This multiple-site, multiple-mode hypothesis offers a framework to study the structural basis of general anesthetic action.
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