Combining Mutations and Electrophysiology to Map Anesthetic Sites on Ligand-Gated Ion Channels.

  title={Combining Mutations and Electrophysiology to Map Anesthetic Sites on Ligand-Gated Ion Channels.},
  author={Stuart A. Forman},
  journal={Methods in enzymology},
  • S. Forman
  • Published 2018
  • Chemistry, Medicine
  • Methods in enzymology
General anesthetics are known to act in part by binding to and altering the function of pentameric ligand-gated ion channels such as nicotinic acetylcholine and γ-aminobutyric acid type A receptors. Combining heterologous expression of the subunits that assemble to form these ion channels, mutagenesis techniques and voltage-clamp electrophysiology have enabled a variety of "structure-function" approaches to questions of where anesthetic binds to these ion channels and how they enhance or… Expand
Elephants in the dark: insights and incongruities in pentameric ligand-gated ion channel models.
  • R. Howard
  • Medicine
  • Journal of molecular biology
  • 2021
This review contextualizes currently available structures in the pLGIC family, focusing on morphology, ligand binding, and gating in three model subfamilies: the prokaryotic channel GLIC, the cation- selective nicotinic acetylcholine receptor, and the anion-selective glycine receptor. Expand
Monod-Wyman-Changeux Allosteric Shift Analysis in Mutant α1β3γ2L GABAA Receptors Indicates Selectivity and Crosstalk among Intersubunit Transmembrane Anesthetic Sites
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X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel
Molecular dynamics simulations, performed on the wild type (WT) and two GLIC mutants, highlight differences in mobility of propofol in its binding site and help to explain these effects, and provide a novel structural framework for the design of general anaesthetics and of allosteric modulators of brain pLGICs. Expand
Barbiturates Bind in the GLIC Ion Channel Pore and Cause Inhibition by Stabilizing a Closed State*♦
The identification of this pore binding site sheds light on the mechanism of barbiturate inhibition of cationic pLGICs and allows the rationalization of several structural and functional features previously observed for barbiturates. Expand
Evidence for Direct Actions of General Anesthetics on an Ion Channel Protein: A New Look at a Unified Mechanism of Action
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General anesthetic actions in vivo strongly attenuated by a point mutation in the GABAA receptor β3 subunit
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  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2003
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Functional sites involved in modulation of the GABAA receptor channel by the intravenous anesthetics propofol, etomidate and pentobarbital
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