ArticlePloS one2015
Positive Allosteric Modulation of Kv Channels by Sevoflurane: Insights into the Structural Basis of Inhaled Anesthetic Action.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- A randomised, double-blind, placebo-controlled study to determine the analgesic efficacy, safety and tolerability of VPX638 administered topically to painful wounds.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair SocietyTrial
- Sevoflurane Inhibits Layer 5 Pyramidal Neurons via Kv1.2-Dependent Modulation of Subthreshold Currents.Journal of neurochemistry · 2026Article
- Insight into molecular and neural mechanisms of general anesthesia from the invertebrate modelZoological research · 2025Review
- How Do Modulators Affect the Orthosteric and Allosteric Binding Pockets?ACS chemical neuroscience · 2022Article
- Concentration-dependent thermodynamic analysis of the partition process of small ligands into proteins.Computational and structural biotechnology journal · 2022Article
- lncRNA KCNQ1OT1 reverses the effect of sevoflurane on hepatocellular carcinoma progression via regulating the miR-29a-3p/CBX3 axis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
- Electromechanical coupling of the Kv1.1 voltage-gated KPflugers Archiv : European journal of physiology · 2020Article
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- 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
- Propofol inhibits prokaryotic voltage-gated NaThe Journal of general physiology · 2018Article
- Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Effects of neoadjuvant chemotherapy on minimum alveolar concentration values of sevoflurane and desflurane in patients with hepatocellular carcinoma complicated with jaundice.Oncology letters · 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
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Inhalational general anesthesia results from the poorly understood interactions of haloethers with multiple protein targets, which prominently includes ion channels in the nervous system. Previously, we reported that the commonly used inhaled anesthetic sevoflurane potentiates the activity of voltage-gated K+ (Kv) channels, specifically, several mammalian Kv1 channels and the Drosophila K-Shaw2 channel. Also, previous work suggested that the S4-S5 linker of K-Shaw2 plays a role in the inhibition of this Kv channel by n-alcohols and inhaled anesthetics. Here, we hypothesized that the S4-S5 linker is also a determinant of the potentiation of Kv1.2 and K-Shaw2 by sevoflurane. Following functional expression of these Kv channels in Xenopus oocytes, we found that converse mutations in Kv1.2 (G329T) and K-Shaw2 (T330G) dramatically enhance and inhibit the potentiation of the corresponding conductances by sevoflurane, respectively. Additionally, Kv1.2-G329T impairs voltage-dependent gating, which suggests that Kv1.2 modulation by sevoflurane is tied to gating in a state-dependent manner. Toward creating a minimal Kv1.2 structural model displaying the putative sevoflurane binding sites, we also found that the positive modulations of Kv1.2 and Kv1.2-G329T by sevoflurane and other general anesthetics are T1-independent. In contrast, the positive sevoflurane modulation of K-Shaw2 is T1-dependent. In silico docking and molecular dynamics-based free-energy calculations suggest that sevoflurane occupies distinct sites near the S4-S5 linker, the pore domain and around the external selectivity filter. We conclude that the positive allosteric modulation of the Kv channels by sevoflurane involves separable processes and multiple sites within regions intimately involved in channel gating.
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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.