Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2009 Mar 20;28412:7889-96. doi: 10.1074/jbc.M806484200.
Show Gene links
Show Anatomy links
Unanticipated structural and functional properties of delta-subunit-containing GABAA receptors.
Kaur KH, Baur R, Sigel E.
???displayArticle.abstract???
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,
Individual properties of the two functional agonist sites in GABA(A) receptors.
2003,
Pubmed
,
Xenbase 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 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,
Positioning of the alpha-subunit isoforms confers a functional signature to gamma-aminobutyric acid type A receptors.
2004,
Pubmed
,
Xenbase Minier,
Techniques: Use of concatenated subunits for the study of ligand-gated ion channels.
2004,
Pubmed Mody,
Extrasynaptic GABAA receptors in the crosshairs of hormones and ethanol.
2008,
Pubmed Mody,
Diversity of inhibitory neurotransmission through GABA(A) receptors.
2004,
Pubmed Mody,
Distinguishing between GABA(A) receptors responsible for tonic and phasic conductances.
2001,
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,
The effect of subunit composition of rat brain GABAA receptors on channel function.
1990,
Pubmed
,
Xenbase Sigel,
Properties of single sodium channels translated by Xenopus oocytes after injection with messenger ribonucleic acid.
1987,
Pubmed
,
Xenbase Sigel,
Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels.
1992,
Pubmed
,
Xenbase Stell,
Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors.
2003,
Pubmed Stell,
Receptors with different affinities mediate phasic and tonic GABA(A) conductances in hippocampal neurons.
2002,
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
