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
2016 Aug 26;29135:18474-83. doi: 10.1074/jbc.M116.738906.
Show Gene links
Show Anatomy links
Toward Understanding Functional Properties and Subunit Arrangement of α4β2δ γ-Aminobutyric Acid, Type A (GABAA) Receptors.
Wongsamitkul N
,
Baur R
,
Sigel E
.
???displayArticle.abstract??? GABAA receptors are pentameric ligand-gated channels mediating inhibitory neurotransmission in the CNS. α4βxδ GABAA receptors are extrasynaptic receptors important for tonic inhibition. The functional properties and subunit arrangement of these receptors are controversial. We predefined subunit arrangement by using subunit concatenation. α4, β2, and δ subunits were concatenated to dimeric, trimeric, and, in some cases, pentameric subunits. We constructed in total nine different receptor pentamers in at least two different ways and expressed them in Xenopus oocytes. The δ subunit was substituted in any of the five positions in the α1β2 receptor. In addition, we investigated all receptors with the 2:2:1 subunit stoichiometry for α4, β2, and δ. Several functional receptors were obtained. Interestingly, all of these receptors had very similar EC50 values for GABA in the presence of the neurosteroid 3α, 21-dihydroxy-5α-pregnan-20-one (THDOC). All functional receptors containing δ subunits were sensitive to 4-chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridin-3-yl]benzamide (DS2). Moreover, none of the receptors was affected by ethanol up to 30 mm These properties recapitulate those of non-concatenated receptors expressed from a cRNA ratio of 1:1:5 coding for α4, β2, and δ subunits. We conclude that the subunit arrangement of α4β2δ GABAA receptors is not strongly predefined but is mostly satisfying the 2:2:1 subunit stoichiometry for α4, β2, and δ subunits and that several subunit arrangements result in receptors with similar functional properties tuned to physiological conditions.
Attwell,
Nonvesicular release of neurotransmitter.
1993, Pubmed
Attwell,
Nonvesicular release of neurotransmitter.
1993,
Pubmed
Barrera,
Atomic force microscopy reveals the stoichiometry and subunit arrangement of the alpha4beta3delta GABA(A) receptor.
2008,
Pubmed
Baumann,
Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement.
2002,
Pubmed
,
Xenbase
Baumann,
Subunit arrangement of gamma-aminobutyric acid type A receptors.
2001,
Pubmed
,
Xenbase
Baumann,
Individual properties of the two functional agonist sites in GABA(A) receptors.
2003,
Pubmed
,
Xenbase
Baur,
Structure of alpha6 beta3 delta GABA(A) receptors and their lack of ethanol sensitivity.
2009,
Pubmed
,
Xenbase
Baur,
Diversity of structure and function of alpha1alpha6beta3delta GABAA receptors: comparison with alpha1beta3delta and alpha6beta3delta receptors.
2010,
Pubmed
,
Xenbase
Baur,
A GABA(A) receptor of defined subunit composition and positioning: concatenation of five subunits.
2006,
Pubmed
,
Xenbase
Belelli,
Extrasynaptic GABAA receptors: form, pharmacology, and function.
2009,
Pubmed
Bianchi,
Neurosteroids shift partial agonist activation of GABA(A) receptor channels from low- to high-efficacy gating patterns.
2003,
Pubmed
Bollan,
The promiscuous role of the epsilon subunit in GABAA receptor biogenesis.
2008,
Pubmed
,
Xenbase
Chang,
Stoichiometry of a recombinant GABAA receptor.
1996,
Pubmed
,
Xenbase
Eaton,
γ-aminobutyric acid type A α4, β2, and δ subunits assemble to produce more than one functionally distinct receptor type.
2014,
Pubmed
,
Xenbase
Farrant,
Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors.
2005,
Pubmed
Farrar,
Stoichiometry of a ligand-gated ion channel determined by fluorescence energy transfer.
1999,
Pubmed
Glykys,
A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol.
2007,
Pubmed
Hartiadi,
High and low GABA sensitivity α4β2δ GABAA receptors are expressed in Xenopus laevis oocytes with divergent stoichiometries.
2016,
Pubmed
,
Xenbase
Jensen,
A study of subunit selectivity, mechanism and site of action of the delta selective compound 2 (DS2) at human recombinant and rodent native GABA(A) receptors.
2013,
Pubmed
,
Xenbase
Jones,
Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression.
1997,
Pubmed
Karim,
Low nanomolar GABA effects at extrasynaptic α4β1/β3δ GABA(A) receptor subtypes indicate a different binding mode for GABA at these receptors.
2012,
Pubmed
,
Xenbase
Kaur,
Unanticipated structural and functional properties of delta-subunit-containing GABAA receptors.
2009,
Pubmed
,
Xenbase
Macdonald,
GABAA receptor channels.
1994,
Pubmed
Minier,
Techniques: Use of concatenated subunits for the study of ligand-gated ion channels.
2004,
Pubmed
Olsen,
International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update.
2008,
Pubmed
Patel,
Stoichiometry of δ subunit containing GABA(A) receptors.
2014,
Pubmed
Patel,
Context-Dependent Modulation of GABAAR-Mediated Tonic Currents.
2016,
Pubmed
Peng,
GABA(A) receptor changes in delta subunit-deficient mice: altered expression of alpha4 and gamma2 subunits in the forebrain.
2002,
Pubmed
Richerson,
Dynamic equilibrium of neurotransmitter transporters: not just for reuptake anymore.
2003,
Pubmed
Shu,
Characteristics of concatemeric GABA(A) receptors containing α4/δ subunits expressed in Xenopus oocytes.
2012,
Pubmed
,
Xenbase
Sigel,
Structure, function, and modulation of GABA(A) receptors.
2012,
Pubmed
Sigel,
Properties of single sodium channels translated by Xenopus oocytes after injection with messenger ribonucleic acid.
1987,
Pubmed
,
Xenbase
Sigel,
The Xenopus oocyte: system for the study of functional expression and modulation of proteins.
2005,
Pubmed
,
Xenbase
Sigel,
Use of concatamers to study GABAA receptor architecture and function: application to delta-subunit-containing receptors and possible pitfalls.
2009,
Pubmed
Sigel,
The effect of subunit composition of rat brain GABAA receptors on channel function.
1990,
Pubmed
,
Xenbase
Sundstrom-Poromaa,
Hormonally regulated alpha(4)beta(2)delta GABA(A) receptors are a target for alcohol.
2002,
Pubmed
,
Xenbase
Sur,
Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus.
1999,
Pubmed
Tretter,
Stoichiometry and assembly of a recombinant GABAA receptor subtype.
1997,
Pubmed
Ueno,
Endogenous subunits can cause ambiguities in the pharmacology of exogenous gamma-aminobutyric acidA receptors expressed in human embryonic kidney 293 cells.
1996,
Pubmed
Wafford,
Novel compounds selectively enhance delta subunit containing GABA A receptors and increase tonic currents in thalamus.
2009,
Pubmed
Wagoner,
Stoichiometry of expressed alpha(4)beta(2)delta gamma-aminobutyric acid type A receptors depends on the ratio of subunit cDNA transfected.
2010,
Pubmed
,
Xenbase
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
Wohlfarth,
Enhanced neurosteroid potentiation of ternary GABA(A) receptors containing the delta subunit.
2002,
Pubmed
Wu,
Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1.
2007,
Pubmed
You,
Identification of a domain in the delta subunit (S238-V264) of the alpha4beta3delta GABAA receptor that confers high agonist sensitivity.
2007,
Pubmed
,
Xenbase
Zheleznova,
alpha1beta2delta, a silent GABAA receptor: recruitment by tracazolate and neurosteroids.
2008,
Pubmed
,
Xenbase
