Open AccessEnhancement of α5-Containing γ-Aminobutyric Acid Type A Receptors by the Nonimmobilizer 1,2-Dichlorohexafluorocyclobutane (F6) Is Abolished by the β3(N265M) Mutation
Author(s) -
Paul M. Burkat,
Chong Lor,
Misha Perouansky,
Robert A. Pearce
Publication year - 2014
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/ane.0000000000000423
Subject(s) - receptor , gabaa receptor , gamma aminobutyric acid , xenopus , aminobutyric acid , microbiology and biotechnology , gabaa rho receptor , biophysics , biology , neuroscience , biochemistry , gene
Modulation of γ-aminobutyric acid type A receptors (GABAARs) by general anesthetics may contribute to their ability to produce amnesia. Receptors containing α5 subunits, which mediate tonic and slow synaptic inhibition, are co-localized with β3 and γ2 subunits in dendritic layers of the hippocampus and are sensitive to low (amnestic) concentrations of anesthetics. Because α5 and β3 subunits influence performance in hippocampus-dependent learning tasks in the presence and absence of general anesthetics, and the experimental inhaled drug 1,2-dichlorohexafluorocyclobutane (F6) impairs hippocampus-dependent learning, we hypothesized that F6 would modulate receptors that incorporate α5 and β3 subunits. We hypothesized further that the β3(N265M) mutation, which controls receptor modulation by general anesthetics, would similarly influence modulation by F6.