ArticleBiophysical journal2011
Isoflurane alters the structure and dynamics of GLIC.
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 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel.eLife · 2021Article
- Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment.Frontiers in medicine · 2020Article
- Multiple functional neurosteroid binding sites on GABAA receptors.PLoS biology · 2019Article
- Ketamine Inhibition of the Pentameric Ligand-Gated Ion Channel GLIC.Biophysical journal · 2017Article
- A membrane-embedded pathway delivers general anesthetics to two interacting binding sites in theThe Journal of biological chemistry · 2017Article
- String method solution of the gating pathways for a pentameric ligand-gated ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The cellular membrane as a mediator for small molecule interaction with membrane proteins.Biochimica et biophysica acta · 2016Article
- Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels.Anesthesiology · 2016Article
- Common Internal Allosteric Network Links Anesthetic Binding Sites in a Pentameric Ligand-Gated Ion Channel.PloS one · 2016Article
- Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.Scientific reports · 2015Article
- The molecular pharmacology of volatile anesthetics.International anesthesiology clinics · 2015Review
- Atomistic models of general anesthetics for use in in silico biological studies.The journal of physical chemistry. B · 2014Article
- Pentameric Ligand-gated Ion Channels : Insights from Computation.Molecular simulation · 2014Article
- Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.Pharmacological reviews · 2014Review
- Propofol binding to the resting state of the gloeobacter violaceus ligand-gated ion channel (GLIC) induces structural changes in the inter- and intrasubunit transmembrane domain (TMD) cavities.The Journal of biological chemistry · 2013Article
- Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia chrysanthemi ligand-gated ion channel (ELIC).The Journal of biological chemistry · 2013Article
- Asymmetric ligand binding facilitates conformational transitions in pentameric ligand-gated ion channels.Journal of the American Chemical Society · 2013Article
- NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR.Biochimica et biophysica acta · 2013Article
- Exploring volatile general anesthetic binding to a closed membrane-bound bacterial voltage-gated sodium channel via computation.PLoS computational biology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pentameric ligand-gated ion channels are targets of general anesthetics. Although the search for discrete anesthetic binding sites has achieved some degree of success, little is known regarding how anesthetics work after the events of binding. Using the crystal structures of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel (GLIC), which is sensitive to a variety of general anesthetics, we performed multiple molecular dynamics simulations in the presence and absence of the general anesthetic isoflurane. Isoflurane bound to several locations within GLIC, including the transmembrane pocket identified crystallographically, the extracellular (EC) domain, and the interface of the EC and transmembrane domains. Isoflurane also entered the channel after the pore was dehydrated in one of the simulations. Isoflurane disrupted the quaternary structure of GLIC, as evidenced in a striking association between the binding and breakage of intersubunit salt bridges in the EC domain. The pore-lining helix experienced lateral and inward radial tilting motion that contributed to the channel closure. Isoflurane binding introduced strong anticorrelated motions between different subunits of GLIC. The demonstrated structural and dynamical modulations by isoflurane aid in the understanding of the underlying mechanism of anesthetic inhibition of GLIC and possibly other homologous pentameric ligand-gated ion channels.
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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.