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J Biol Chem
2009 Mar 20;28412:7889-96. doi: 10.1074/jbc.M806484200.
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Unanticipated structural and functional properties of delta-subunit-containing GABAA receptors.
Kaur KH
,
Baur R
,
Sigel E
.
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GABA(A) receptors mediate inhibitory neurotransmission in the mammalian brain via synaptic and extrasynaptic receptors. The delta (delta)-subunit-containing receptors are expressed exclusively extra-synaptically and mediate tonic inhibition. In the present study, we were interested in determining the architecture of receptors containing the delta-subunit. To investigate this, we predefined the subunit arrangement by concatenation. We prepared five dual and three triple concatenated subunit constructs. These concatenated dual and triple constructs were used to predefine nine different GABA(A) receptor pentamers. These pentamers composed of alpha(1)-, beta(3)-, and delta-subunits were expressed in Xenopus oocytes and maximal currents elicited in response to 1 mm GABA were determined in the presence and absence of THDOC (3alpha, 21-dihydroxy-5alpha-pregnane-20-one). beta(3)-alpha(1)-delta/alpha(1)-beta(3) and beta(3)-alpha(1)-delta/beta(3)-alpha(1) resulted in the expression of large currents in response to GABA. Interestingly, the presence of the neurosteroid THDOC uncovered alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors, additionally. The functional receptors were characterized in detail using the agonist GABA, THDOC, Zn(2+), and ethanol and their properties were compared with those of non-concatenated alpha(1)beta(3) and alpha(1)beta(3)delta receptors. Each concatenated receptor isoform displayed a specific set of properties, but none of them responded to 30 mm ethanol. We conclude from the investigated receptors that delta can assume multiple positions in the receptor pentamer. The GABA dose-response properties of alpha(1)-beta(3)-alpha(1)/beta(3)-delta and beta(3)-alpha(1)-delta/alpha(1)-beta(3) match most closely the properties of non-concatenated alpha(1)beta(3)delta receptors. Furthermore, we show that the delta-subunit can contribute to the formation of an agonist site in alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors.
Amin,
GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital.
1993, Pubmed,
Xenbase
Amin,
GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital.
1993,
Pubmed
,
Xenbase
Araujo,
Absence of association between delta and gamma2 subunits in native GABA(A) receptors from rat brain.
1998,
Pubmed
Barnard,
International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function.
1998,
Pubmed
Barrera,
Atomic force microscopy reveals the stoichiometry and subunit arrangement of the alpha4beta3delta GABA(A) receptor.
2008,
Pubmed
Baumann,
Subunit arrangement of gamma-aminobutyric acid type A receptors.
2001,
Pubmed
,
Xenbase
Baumann,
Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement.
2002,
Pubmed
,
Xenbase
Baumann,
Individual properties of the two functional agonist sites in GABA(A) receptors.
2003,
Pubmed
,
Xenbase
Baur,
A GABA(A) receptor of defined subunit composition and positioning: concatenation of five subunits.
2006,
Pubmed
,
Xenbase
Bianchi,
Neurosteroids shift partial agonist activation of GABA(A) receptor channels from low- to high-efficacy gating patterns.
2003,
Pubmed
Boileau,
The relative amount of cRNA coding for gamma2 subunits affects stimulation by benzodiazepines in GABA(A) receptors expressed in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Bollan,
The promiscuous role of the epsilon subunit in GABAA receptor biogenesis.
2008,
Pubmed
,
Xenbase
Borghese,
The delta subunit of gamma-aminobutyric acid type A receptors does not confer sensitivity to low concentrations of ethanol.
2006,
Pubmed
,
Xenbase
Cope,
GABAA receptor-mediated tonic inhibition in thalamic neurons.
2005,
Pubmed
Farrant,
Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors.
2005,
Pubmed
Feng,
Proton modulation of alpha 1 beta 3 delta GABAA receptor channel gating and desensitization.
2004,
Pubmed
Fisher,
Single channel properties of recombinant GABAA receptors containing gamma 2 or delta subtypes expressed with alpha 1 and beta 3 subtypes in mouse L929 cells.
1997,
Pubmed
Glykys,
A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol.
2007,
Pubmed
Hadley,
Rat alpha6beta2delta GABAA receptors exhibit two distinct and separable agonist affinities.
2007,
Pubmed
,
Xenbase
Hanchar,
Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activity.
2005,
Pubmed
,
Xenbase
Herd,
Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors.
2007,
Pubmed
Jechlinger,
Subunit composition and quantitative importance of hetero-oligomeric receptors: GABAA receptors containing alpha6 subunits.
1998,
Pubmed
Jia,
An extrasynaptic GABAA receptor mediates tonic inhibition in thalamic VB neurons.
2005,
Pubmed
Jones,
Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression.
1997,
Pubmed
Krishek,
Interaction of H+ and Zn2+ on recombinant and native rat neuronal GABAA receptors.
1998,
Pubmed
,
Xenbase
Macdonald,
GABAA receptor channels.
1994,
Pubmed
Maguire,
Ovarian cycle-linked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety.
2005,
Pubmed
Mertens,
GABAA receptor populations with novel subunit combinations and drug binding profiles identified in brain by alpha 5- and delta-subunit-specific immunopurification.
1993,
Pubmed
Minier,
Techniques: Use of concatenated subunits for the study of ligand-gated ion channels.
2004,
Pubmed
Minier,
Positioning of the alpha-subunit isoforms confers a functional signature to gamma-aminobutyric acid type A receptors.
2004,
Pubmed
,
Xenbase
Mody,
Distinguishing between GABA(A) receptors responsible for tonic and phasic conductances.
2001,
Pubmed
Mody,
Diversity of inhibitory neurotransmission through GABA(A) receptors.
2004,
Pubmed
Mody,
Extrasynaptic GABAA receptors in the crosshairs of hormones and ethanol.
2008,
Pubmed
Nusser,
Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells.
2002,
Pubmed
Quirk,
Characterisation of delta-subunit containing GABAA receptors from rat brain.
1995,
Pubmed
Rabow,
From ion currents to genomic analysis: recent advances in GABAA receptor research.
1995,
Pubmed
Saxena,
Assembly of GABAA receptor subunits: role of the delta subunit.
1994,
Pubmed
Saxena,
Properties of putative cerebellar gamma-aminobutyric acid A receptor isoforms.
1996,
Pubmed
Scimemi,
Tonic GABA(A) receptor-mediated currents in human brain.
2006,
Pubmed
Sieghart,
Subunit composition, distribution and function of GABA(A) receptor subtypes.
2002,
Pubmed
Sigel,
Properties of single sodium channels translated by Xenopus oocytes after injection with messenger ribonucleic acid.
1987,
Pubmed
,
Xenbase
Sigel,
The effect of subunit composition of rat brain GABAA receptors on channel function.
1990,
Pubmed
,
Xenbase
Sigel,
Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels.
1992,
Pubmed
,
Xenbase
Stell,
Receptors with different affinities mediate phasic and tonic GABA(A) conductances in hippocampal neurons.
2002,
Pubmed
Stell,
Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors.
2003,
Pubmed
Stórustovu,
Pharmacological characterization of agonists at delta-containing GABAA receptors: Functional selectivity for extrasynaptic receptors is dependent on the absence of gamma2.
2006,
Pubmed
,
Xenbase
Sur,
Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus.
1999,
Pubmed
Wallner,
Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans.
2003,
Pubmed
,
Xenbase
Wei,
Low ethanol concentrations selectively augment the tonic inhibition mediated by delta subunit-containing GABAA receptors in hippocampal neurons.
2004,
Pubmed
Whiting,
Molecular and functional diversity of the expanding GABA-A receptor gene family.
1999,
Pubmed
Wohlfarth,
Enhanced neurosteroid potentiation of ternary GABA(A) receptors containing the delta subunit.
2002,
Pubmed
Zheleznova,
alpha1beta2delta, a silent GABAA receptor: recruitment by tracazolate and neurosteroids.
2008,
Pubmed
,
Xenbase
Zhu,
Delta subunit inhibits neurosteroid modulation of GABAA receptors.
1996,
Pubmed
