Volume 868, Issue 1 p. 645-653

Molecular and Functional Diversity of the Expanding GABA-A Receptor Gene Family

PAUL J. WHITING

PAUL J. WHITING

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

aCorresponding author. Phone: 1279-440535; fax: 1279-440712; e-mail: [email protected]

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TIMOTHY P. BONNERT

TIMOTHY P. BONNERT

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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RUTH M. MCKERNAN

RUTH M. MCKERNAN

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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SOPHIE FARRAR

SOPHIE FARRAR

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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BEATRICE LE BOURDELLES

BEATRICE LE BOURDELLES

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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ROBERT P. HEAVENS

ROBERT P. HEAVENS

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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DAVID W. SMITH

DAVID W. SMITH

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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LOUISE HEWSON

LOUISE HEWSON

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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MICHAEL R. RIGBY

MICHAEL R. RIGBY

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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DALIP J. S. SIRINATHSINGHJI

DALIP J. S. SIRINATHSINGHJI

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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SALLY A. THOMPSON

SALLY A. THOMPSON

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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KEITH A. WAFFORD

KEITH A. WAFFORD

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK

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First published: 06 February 2006
Citations: 263

Abstract

ABSTRACT: Fast inhibitory neurotransmission in the mammalian CNS is mediated primarily by the neurotransmitter γ-aminobutyric acid (GABA), which, upon binding to its receptor, leads to opening of the intrinsic ion channel, allowing chloride to enter the cell. Over the past 10 years it has become clear that a family of GABA-A receptor subtypes exists, generated through the coassembly of polypeptides selected from α1-α6, β1-β3, γ1-γ3, δ, ɛ, and π to form what is most likely a pentomeric macromolecule. The gene transcripts, and indeed the polypeptides, show distinct patterns of temporal and spatial expression, such that the GABA-A receptor subtypes have a defined localization that presumably reflects their physiological role. A picture is beginning to emerge of the properties conferred to receptor subtypes by the different subunits; these include different functional properties, differential modulation by protein kinases, and the targeting to different membrane compartments. These properties presumably underlie the different physiological roles of the various receptor subtypes. Recently we have identified a further member of the GABA-A receptor gene family, which we have termed θ, which appears to be most closely related to the β subunits. The structure, function, and distribution of θ-containing receptors, and receptors containing the recently reported ɛ subunit, are described.