ArticlePLoS computational biology2018
Binding of the general anesthetic sevoflurane to ion channels.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- General anesthesia and depth of anesthesia (DoA) evaluation methods in laboratory animals: a comprehensive review.Veterinary research communications · 2026Review
- Sevoflurane Inhibits Layer 5 Pyramidal Neurons via Kv1.2-Dependent Modulation of Subthreshold Currents.Journal of neurochemistry · 2026Article
- Genome x Environment analysis of Sudden Unexpected Infant Death unveils etiologic heterogeneity and strong cannabis and genetic disease risks.medRxiv : the preprint server for health sciences · 2025Article
- The binding and mechanism of a positive allosteric modulator of Kv3 channels.Nature communications · 2024Article
- The Modulation by Anesthetics and Analgesics of Respiratory Rhythm in the Nervous System.Current neuropharmacology · 2024Review
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol.Molecular neurobiology · 2023Article
- Identifying c-fos Expression as a Strategy to Investigate the Actions of General Anesthetics on the Central Nervous System.Current neuropharmacology · 2022Review
- Concentration-dependent thermodynamic analysis of the partition process of small ligands into proteins.Computational and structural biotechnology journal · 2022Article
- Dendritic spine remodeling and plasticity under general anesthesia.Brain structure & function · 2021Review
- Towards Quantum-Chemical Modeling of the Activity of Anesthetic Compounds.International journal of molecular sciences · 2021Review
- Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated KBritish journal of pharmacology · 2020Article
- A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol.Frontiers in cellular neuroscience · 2020Article
- Hydrophobic Drug/Toxin Binding Sites in Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The direct-site hypothesis assumes general anesthetics bind ion channels to impact protein equilibrium and function, inducing anesthesia. Despite advancements in the field, a first principle all-atom demonstration of this structure-function premise is still missing. We focus on the clinically used sevoflurane interaction to anesthetic-sensitive Kv1.2 mammalian channel to resolve if sevoflurane binds protein's well-characterized open and closed structures in a conformation-dependent manner to shift channel equilibrium. We employ an innovative approach relying on extensive docking calculations and free-energy perturbation of all potential binding sites revealed by the latter, and find sevoflurane binds open and closed structures at multiple sites under complex saturation and concentration effects. Results point to a non-trivial interplay of site and conformation-dependent modes of action involving distinct binding sites that increase channel open-probability at diluted ligand concentrations. Given the challenge in exploring more complex processes potentially impacting channel-anesthetic interaction, the result is revealing as it demonstrates the process of multiple anesthetic binding events alone may account for open-probability shifts recorded in measurements.
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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.