GABAa receptor α and γ subunits shape synaptic currents via different mechanisms

Dixon, Christine, Sah, Pankaj, Lynch, Joseph W. and Keramidas, Angelo (2014) GABAa receptor α and γ subunits shape synaptic currents via different mechanisms. Journal of Biological Chemistry, 289 9: 5399-5411. doi:10.1074/jbc.M113.514695

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Author Dixon, Christine
Sah, Pankaj
Lynch, Joseph W.
Keramidas, Angelo
Title GABAa receptor α and γ subunits shape synaptic currents via different mechanisms
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2014-02-28
Year available 2014
Sub-type Article (original research)
DOI 10.1074/jbc.M113.514695
Open Access Status DOI
Volume 289
Issue 9
Start page 5399
End page 5411
Total pages 13
Place of publication Bethesda, MD United States
Publisher American Society for Biochemistry and Molecular Biology Inc.
Collection year 2015
Language eng
Subject 1303 Specialist Studies in Education
1307 Cell Biology
1312 Molecular Biology
Abstract Synaptic GABAA receptors (GABAARs) mediate most of the inhibitory neurotransmission in the brain. The majority of these receptors are comprised of α1, β2, and γ2 subunits. The amygdala, a structure involved in processing emotional stimuli, expresses α2 and γ1 subunits at high levels. The effect of these subunits on GABA AR-mediated synaptic transmission is not known. Understanding the influence of these subunits on GABAAR-mediated synaptic currents may help in identifying the roles and locations of amygdala synapses that contain these subunits. Here, we describe the biophysical and synaptic properties of pure populations of α1β2γ2, α2β2γ2, α1β2γ1 and α2β2γ1 GABAARs. Their synaptic properties were examined in engineered synapses, whereas their kinetic properties were studied using rapid agonist application, and single channel recordings. All macropatch currents activated rapidly (<1 ms) and deactivated as a function of the α-subunit, with α2-containing GABA ARs consistently deactivating ∼10-fold more slowly. Single channel analysis revealed that the slower current decay of α2-containing GABAARs was due to longer burst durations at low GABA concentrations, corresponding to a ∼4-fold higher affinity for GABA. Synaptic currents revealed a different pattern of activation and deactivation to that of macropatch data. The inclusion of α2 and γ1 subunits slowed both the activation and deactivation rates, suggesting that receptors containing these subunits cluster more diffusely at synapses. Switching the intracellular domains of the γ2 and γ1 subunits substantiated this inference. Because this region determines post-synaptic localization, we hypothesize that GABA ARs containing γ1 and γ2 use different mechanisms for synaptic clustering.
Keyword Chloride channels
Cys Loop Receptors
Gaba Receptors
Kinetics
Synapses
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
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