Article abstract
Nature Neuroscience 10, 40 - 48 (2007)
Published online: 10 December 2006 | doi:10.1038/nn1813
A new naturally occurring GABAA receptor subunit partnership with high sensitivity to ethanol
Joseph Glykys1,5, Zechun Peng2,5, Dev Chandra3, Gregg E Homanics3, Carolyn R Houser2,4 & Istvan Mody1
Abstract
According to the rules of GABAA receptor (GABAAR) subunit assembly, 
4 and 6 subunits are considered to be the natural partners of 
subunits. These GABAARs are a preferred target of low, sobriety-impairing concentrations of ethanol. Here we demonstrate a new naturally occurring GABAAR subunit partnership: subunits of hippocampal interneurons are coexpressed and colocalized with 1 subunits, but not with 4, 6 or any other subunits. Ethanol potentiates the tonic inhibition mediated by such native 1/ GABAARs in wild-type and in 4 subunit–deficient (Gabra4-/-) mice, but not in subunit–deficient (Gabrd-/-) mice. We also ruled out any compensatory upregulation of 6 subunits that might have accounted for the ethanol effect in Gabra4-/- mice. Thus, 1/ subunit assemblies represent a new neuronal GABAAR subunit partnership present in hippocampal interneurons, mediate tonic inhibitory currents and are highly sensitive to low concentrations of ethanol.
- Interdepartmental PhD Program for Neuroscience and Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, California 90095, USA.
- Department of Neurobiology, David Geffen School of Medicine at the University of California, Los Angeles, California 90095, USA.
- Departments of Anesthesiology and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
- Research Service, VA Greater Los Angeles Healthcare System, West Los Angeles, Los Angeles, California 90073, USA.
- These authors contributed equally to this work.
Correspondence to: Istvan Mody1 e-mail: mody@ucla.edu
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