GABAA Receptor and Subunits Shape Synaptic Currents via Different ...

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Aug 28, 2013 - Results: 2 subunits increased GABA affinity thereby slowing current deactivation; ... Synaptic GABAA receptors (GABAARs) mediate most of the.
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 289, NO. 9, pp. 5399 –5411, February 28, 2014 © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.

GABAA Receptor ␣ and ␥ Subunits Shape Synaptic Currents via Different Mechanisms* Received for publication, August 28, 2013, and in revised form, January 13, 2014 Published, JBC Papers in Press, January 14, 2014, DOI 10.1074/jbc.M113.514695

Christine Dixon, Pankaj Sah, Joseph W. Lynch1, and Angelo Keramidas2 From the Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia 4072 Background: GABAAR ␣2 and ␥1 subunits are highly expressed in amygdala but their influence on synaptic currents is unknown. Results: ␣2 subunits increased GABA affinity thereby slowing current deactivation; ␥1 subunits reduced synaptic receptor clustering. Conclusion: These subunits may differentially shape synaptic kinetics. Significance: Understanding how ␣2 and ␥1 subunits shape synaptic currents may help us understand amygdala processing mechanisms. Synaptic GABAA receptors (GABAARs) mediate most of the inhibitory neurotransmission in the brain. The majority of these receptors are comprised of ␣1, ␤2, and ␥2 subunits. The amygdala, a structure involved in processing emotional stimuli, expresses ␣2 and ␥1 subunits at high levels. The effect of these subunits on GABAAR-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 ␣1␤2␥2, ␣2␤2␥2, ␣1␤2␥1 and ␣2␤2␥1 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 (