Cited by 56Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchIon channel regulation and function

Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics

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Howard, Rebecca J., Trudell, James R., Harris, R. Adron·2014·Pharmacological Reviews

Abstract

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.

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  • Anesthetic actions on pLGICs are not limited to GABAA receptors and are not unique to mammals.

    “Anesthetic actions on pLGICs are not limited solely to GABAA receptors [41–44] and the modulatory actions of anesthetics on pLGIC family members are not unique to mammalian systems [45, 46].”

    From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [43]

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Authors
Howard, R. J., Trudell, J. R., & Harris, R. A.
Affiliations
Skidmore College (US)
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2014-04
Volume
66
Issue
2
Pages
396-412
ISSN
0031-6997 (ISSN-L)
OpenAlex
W2124771139
Cited by
56
References
185
Citations by year
2026: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 12 · 2016: 9 · 2015: 5 · 2014: 6
FWCI
1.01
Type
journal article
Language
en
Open access
Locations
  • Pharmacological Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Creative Matter (Skidmore College) (submittedVersion)
Funders
  • Skidmore College
  • National Institutes of Health (5r01aa006399-36, AA06399)
  • National Institute on Alcohol Abuse and Alcoholism (R01-AA006399, R01-AA06399, R01AA013378, R01AA020980)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
pentameric ligand-gated ion channels, general anesthetics, alcohol, allosteric modulation, ion channel structure, crystal structure, anesthetic binding, ion channel function
MeSH terms
Alcohols, Animals, Behavior, Animal, Binding Sites, Humans, Ligands, Protein Binding, Protein Conformation, Drug Design, Crystallography, X-Ray, Anesthetics, General, Alcohol-Related Disorders, Molecular Dynamics Simulation, Ligand-Gated Ion Channels

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