ArticleProceedings of the National Academy of Sciences of the United States of America2010
Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- Volatile anaesthetics modulate voltage-gated sodium channel function at a site directly linked to channel gating.Nature communications · 2026Article
- A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.Science advances · 2025Article
- Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer's disease models.Translational neurodegeneration · 2024Article
- A bupropion modulatory site in the Gloeobacter violaceus ligand-gated ion channel.Biophysical journal · 2024Article
- Identifying c-fos Expression as a Strategy to Investigate the Actions of General Anesthetics on the Central Nervous System.Current neuropharmacology · 2022Review
- Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design.Frontiers in pharmacology · 2022Review
- Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel.eLife · 2021Article
- Reduction in hypoxia-reoxygenation-induced myocardial mitochondrial damage with exogenous methane.Journal of cellular and molecular medicine · 2021Article
- [Inhalational anesthetics].Der Anaesthesist · 2021Article
- Ion Channels in Anesthesia.Advances in experimental medicine and biology · 2021Article
- Menthol Binding to the Human α4β2 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane.The journal of physical chemistry. B · 2020Article
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Binding of the general anesthetic sevoflurane to ion channels.PLoS computational biology · 2018Article
- Anesthetic-sensitive ion channel modulation is associated with a molar water solubility cut-off.BMC pharmacology & toxicology · 2018Article
- Pharmacological characterization of the neurotrophic sesquiterpene jiadifenolide reveals a non-convulsant signature and potential for progression in neurodegenerative disease studies.Biochemical pharmacology · 2018Article
- Spontaneous respiratory plasticity following unilateral high cervical spinal cord injury in behaving rats.Experimental neurology · 2018Article
- Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.Biochimica et biophysica acta. Biomembranes · 2018Review
- Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions.European journal of pharmacology · 2018Article
5 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
An extensive search for isoflurane binding sites in the nicotinic acetylcholine receptor (nAChR) and the proton gated ion channel from Gloebacter violaceus (GLIC) has been carried out based on molecular dynamics (MD) simulations in fully hydrated lipid membrane environments. Isoflurane introduced into the aqueous phase readily partitions into the lipid membrane and the membrane-bound protein. Specifically, isoflurane binds persistently to three classes of sites in the nAChR transmembrane domain: (i) An isoflurane dimer occludes the pore, contacting residues identified by previous mutagenesis studies; analogous behavior is observed in GLIC. (ii) Several nAChR subunit interfaces are also occupied, in a site suggested by photoaffinity labeling and thought to positively modulate the receptor; these sites are not occupied in GLIC. (iii) Isoflurane binds to the subunit centers of both nAChR alpha chains and one of the GLIC chains, in a site that has had little experimental targeting. Interpreted in the context of existing structural and physiological data, the present MD results support a multisite model for the mechanism of receptor-channel modulation by anesthetics.
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