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

J. Biol. Chem., Vol. 281, Issue 47, 35699-35708, November 24, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/47/35699    most recent M605590200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luu, T. Articles by Tierney, M. L. Search for Related Content PubMed PubMed Citation Articles by Luu, T. Articles by Tierney, M. L. Social Bookmarking                      What's this?

GABA Increases both the Conductance and Mean Open Time of Recombinant GABA_A Channels Co-expressed with GABARAP^*

From the Division of Molecular Bioscience, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 0200, Australia

The single channel properties of recombinant -aminobutyric acid type A (GABA_A) receptors co-expressed with the trafficking protein GABARAP were investigated using membrane patches in the outside-out patch clamp configuration from transiently transfected L929 cells. In control cells expressing receptors alone, GABA activated single channels whose main conductance was 30 picosiemens (pS) with a subconductance state of 20 pS, and increasing the GABA concentration did not alter their conductance. In contrast, when GABA_A receptors were co-expressed with GABARAP, the GABA-activated single channels displayed multiple, high conductances (40 pS), and GABA (10 µM) was able to increase their conductance, up to a maximum of 60 pS. The mean open time of GABA-activated channels in control cells expressing receptors alone was 2.3 ± 0.1 ms for the main 30-pS channel and shorter for the subconductance state (20 pS, 0.8 ± 0.1 ms). Similar values were measured for the 30- and 20-pS channels active in patches from cells co-expressing GABARAP. However higher conductance channels (40 pS) remained open longer, irrespective of whether GABA or GABA plus diazepam activated them. Plotting mean open times against mean conductances revealed a linear relationship between these two parameters. Since high GABA concentrations increase both the maximum single channel conductance and mean open time of GABA_A channels co-expressed with GABARAP, trafficking processes must influence ion channel properties. This suggests that the organization of extrasynaptic GABA_A receptors may provide a range of distinct inhibitory currents in the brain and, further, provide differential drug responses.

Received for publication, June 12, 2006 , and in revised form, August 29, 2006.

^* This work was funded by National Health and Medical Research Council of Australia Grant 268046. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

We dedicate this paper to the memory of Professor Peter Gage.

¹ To whom correspondence should be addressed. Tel.: 61-2-6125-2593; Fax: 61-2-6125-4761; E-mail: Louise.Tierney{at}anu.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. L. Cook, R. N. Re, D. L. deHaro, J. M. Abadie, M. Peters, and J. Alam The Trafficking Protein GABARAP Binds to and Enhances Plasma Membrane Expression and Function of the Angiotensin II Type 1 Receptor Circ. Res., June 20, 2008; 102(12): 1539 - 1547. [Abstract] [Full Text] [PDF]

				H. Sun, X.-Q. Hu, M. B. Emerit, J. C. Schoenebeck, C. E. Kimmel, R. W. Peoples, A. Miko, and L. Zhang Modulation of 5-HT3 receptor desensitization by the light chain of microtubule-associated protein 1B expressed in HEK 293 cells J. Physiol., February 1, 2008; 586(3): 751 - 762. [Abstract] [Full Text] [PDF]

				S.-y. Kawaguchi and T. Hirano Sustained Structural Change of GABAA Receptor-Associated Protein Underlies Long-Term Potentiation at Inhibitory Synapses on a Cerebellar Purkinje Neuron J. Neurosci., June 20, 2007; 27(25): 6788 - 6799. [Abstract] [Full Text] [PDF]