Extrasynaptic GABAA receptors: form, pharmacology, and function.

Full Abstract

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABA(A) and GABA(B) receptors. Recently, a novel form of GABA(A) receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABA(A) receptors underlie classical "phasic" GABA(A) receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABA(A) receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABA(A) receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This mini-symposium review highlights ongoing work examining the properties of recombinant and native extrasynaptic GABA(A) receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABA(A) receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.

Author information

Author/s: Belelli, Delia (D); Harrison, Neil L (NL); Maguire, Jamie (J); Macdonald, Robert L (RL); Walker, Matthew C (MC); Cope, David W (DW);

Affiliation: Division of Medical Sciences, Centre for Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom.

Grants: 71436 (Agency:Wellcome Trust) ; AA16393 (Agency:NIAAA NIH HHS) ; C509923 (Agency:Biotechnology and Biological Sciences Research Council) ; G0400136 (Agency:Medical Research Council) ; GM45129 (Agency:NIGMS NIH HHS) ; GM61925 (Agency:NIGMS NIH HHS) ; MH076994 (Agency:NIMH NIH HHS) ; NS33300 (Agency:NINDS NIH HHS) ; NS51590 (Agency:NINDS NIH HHS) ; WT083163MF (Agency:Wellcome Trust)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 41) : pp 12757-63

Dates: Created 2009/10/15; Completed 2009/10/30;

PMID: 19828786, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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