ArticleBiophysical journal2011
Molecular mapping of general anesthetic sites in a voltage-gated ion channel.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Sevoflurane Inhibits Layer 5 Pyramidal Neurons via Kv1.2-Dependent Modulation of Subthreshold Currents.Journal of neurochemistry · 2026Article
- Relevance of Cortical and Hippocampal Interneuron Functional Diversity to General Anesthetic Mechanisms: A Narrative Review.Frontiers in synaptic neuroscience · 2021Review
- Hydrophobic Drug/Toxin Binding Sites in Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Binding of the general anesthetic sevoflurane to ion channels.PLoS computational biology · 2018Article
- Regulatory Effect of General Anesthetics on Activity of Potassium Channels.Neuroscience bulletin · 2018Review
- Protonation state of inhibitors determines interaction sites within voltage-gated sodium channels.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Sites and Functional Consequence of Alkylphenol Anesthetic Binding to Kv1.2 Channels.Molecular neurobiology · 2018Article
- Concentration-Dependent Binding of Small Ligands to Multiple Saturable Sites in Membrane Proteins.Scientific reports · 2017Article
- Isoflurane modulates activation and inactivation gating of the prokaryotic NaThe Journal of general physiology · 2017Article
- Biophysical studies of cholesterol effects on chromatin.Journal of lipid research · 2017Article
- Gambierol and n-alkanols inhibit Shaker Kv channel via distinct binding sites outside the K(+) pore.Toxicon : official journal of the International Society on Toxinology · 2016Article
- Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels.Neuropharmacology · 2016Article
- Alkanols inhibit voltage-gated K(+) channels via a distinct gating modifying mechanism that prevents gate opening.Scientific reports · 2015Article
- Mechanistic Insights into the Modulation of Voltage-Gated Ion Channels by Inhalational Anesthetics.Biophysical journal · 2015Review
- Positive Allosteric Modulation of Kv Channels by Sevoflurane: Insights into the Structural Basis of Inhaled Anesthetic Action.PloS one · 2015Article
- Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer properties.The Journal of general physiology · 2014Article
- Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Article
- Insight into the modulation of Shaw2 Kv channels by general anesthetics: structural and functional studies of S4-S5 linker and S6 C-terminal peptides in micelles by NMR.Biochimica et biophysica acta · 2013Article
- Novel activation of voltage-gated K(+) channels by sevoflurane.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Several voltage-gated ion channels are modulated by clinically relevant doses of general anesthetics. However, the structural basis of this modulation is not well understood. Previous work suggested that n-alcohols and inhaled anesthetics stabilize the closed state of the Shaw2 voltage-gated (Kv) channel (K-Shaw2) by directly interacting with a discrete channel site. We hypothesize that the inhibition of K-Shaw2 channels by general anesthetics is governed by interactions between binding and effector sites involving components of the channel's activation gate. To investigate this hypothesis, we applied Ala/Val scanning mutagenesis to the S4-S5 linker and the post-PVP S6 segment, and conducted electrophysiological analysis to evaluate the energetic impact of the mutations on the inhibition of the K-Shaw2 channel by 1-butanol and halothane. These analyses identified residues that determine an apparent binding cooperativity and residue pairs that act in concert to modulate gating upon anesthetic binding. In some instances, due to their critical location, key residues also influence channel gating. Complementing these results, molecular dynamics simulations and in silico docking experiments helped us visualize possible anesthetic sites and interactions. We conclude that the inhibition of K-Shaw2 by general anesthetics results from allosteric interactions between distinct but contiguous binding and effector sites involving inter- and intrasubunit interfaces.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.