Correlation between synaptic GABA-A receptor subunit composition and the kinetics and pharmacology of GABA-A receptor-mediated synaptic currents

Abstract

Event Abstract Back to Event Correlation between synaptic GABA-A receptor subunit composition and the kinetics and pharmacology of GABA-A receptor-mediated synaptic currents Mark D. Eyre1* and Zoltán Nusser1 1 Hungarian Academy of Sciences, Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungary Three different subunit types (α, β and γ) are required to compose most functional synaptic GABA-A receptors (GABA-A R), forming a stoichiometry of two α, two β and one γ subunits. Different subunit isoforms confer distinct receptor kinetics and pharmacological modulation when expressed in HEK cells. How these functional properties depend on the subunit composition in GABAergic synapses is less clear. Here we used whole-cell patch clamp recordings of miniature IPSCs in acute slices from identified neurons to address the relationship between IPSC kinetics, benzodiazepine pharmacology and synaptic subunit expression. The benzodiazepine agonist zolpidem has ~100-fold greater affinity for α1-containing GABA-A Rs compared to α2 and α3-containing ones, making it an amenable tool (at 100 nM) for studying the subunit composition of synaptic GABA-A Rs. First, we investigated cerebellar stellate cells that contain only the α1 as α subunit and main olfactory bulb (MOB) granule cells that express only the α2 as α subunit in their synapses. mIPSCs in stellate cells had an average weighted decay time constant (tw) of 4.8±0.2 ms and zolpidem slowed the decay time constant by 43.8±1.3%. In contrast, mIPSCs in granule cells were 3-fold slower (tw=14.2±0.8 ms) and showed no slowing of the decay by zolpidem (-4.9±5.5%). Next, we investigated mIPSCs in cells that express multiple synaptic α and β subunits. Deep short axon cells (dSACs) and external tufted cells (ETCs) of the MOB heterogeneously express the α1/α3 and β2/β3 subunits. Our results demonstrate that their mIPSC decay times were slower (ETCs tw=8.1±1.8 ms; dSACs tw=7.1±0.9 ms) than those of stellate cells. The zolpidem sensitivity of mIPSC decays in these cells will be compared to the immunofluorescent labeling of α1, α3, β2 and b3 subunits. Our pharmacological and kinetic results are consistent with the subunit composition of synaptic GABA-A Rs of these cells. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Cellular neuroscience Citation: Eyre MD and Nusser Z (2010). Correlation between synaptic GABA-A receptor subunit composition and the kinetics and pharmacology of GABA-A receptor-mediated synaptic currents. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00036 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Apr 2010; Published Online: 19 Apr 2010. * Correspondence: Mark D Eyre, Hungarian Academy of Sciences, Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, Hungary, eyre@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mark D Eyre Zoltán Nusser Google Mark D Eyre Zoltán Nusser Google Scholar Mark D Eyre Zoltán Nusser PubMed Mark D Eyre Zoltán Nusser Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.