HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 102/4/2312    most recent 00227.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Belujon, P. Articles by Taupignon, A. I. PubMed PubMed Citation Articles by Belujon, P. Articles by Taupignon, A. I.

RESEARCH-ARTICLE

Inhibitory Transmission in Locus Coeruleus Neurons Expressing GABA_A Receptor Epsilon Subunit Has a Number of Unique Properties

¹University Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche, Bordeaux, France; ²Department of Pharmacology, School of Medicine, University of the Basque Country, Vizcaya, Spain; and ³Leeds Institute of Genetics, Therapeutics and Health (LIGHT), University of Leeds, Leeds, United Kingdom

Submitted 13 March 2009; accepted in final form 21 July 2009

ABSTRACT

Fast inhibitory synaptic transmission in the brain relies on ionotropic GABA_A receptors (GABA_AR). Eighteen genes code for GABA_AR subunits, but little is known about the subunit. Our aim was to identify the synaptic transmission properties displayed by native receptors incorporating . Immunogold localization detected at synaptic sites on locus coeruleus (LC) neurons. In situ hybridization revealed prominent signals from , and mRNAs, some low β1 and β3 signals, and no signal. Using in vivo extracellular and in vitro patch-clamp recordings in LC, we established that neuron firing rates, GABA-activated currents, and mIPSC charge were insensitive to the benzodiazepine flunitrazepam (FLU), in agreement with the characteristics of recombinant receptors including an subunit. Surprisingly, LC provided binding sites for benzodiazepines, and GABA-induced currents were potentiated by diazepam (DZP) in the micromolar range. A number of GABA_AR ligands significantly potentiated GABA-induced currents, and zinc ions were only active at concentrations above 1 µM, further indicating that receptors were not composed of only and β subunits, but included an subunit. In contrast to recombinant receptors including an subunit, GABA_AR in LC showed no agonist-independent opening. Finally, we determined that mIPSCs, as well as ensemble currents induced by ultra-fast GABA application, exhibited surprisingly slow rise times. Our work thus defines the signature of native GABA_AR with a subunit composition including : differential sensitivity to FLU and DZP and slow rise time of currents. We further propose that _3, β_1/3, and subunits compose GABA_AR in LC.