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.
???displayArticle.abstract???
1. Whole-cell currents were recorded from Xenopus laevis oocytes expressing wild-type and mutant recombinant GABAA receptors to locate a binding site for Zn2+ ions in the beta 3 subunit. 2. The Cl(-)-selective current, spontaneously gated by beta 3 subunit homomers, was enhanced by pentobarbitone and inhibited by picrotoxinin. The potencies of these agents were minimally affected by mutating histidine (H) 292 to alanine (A) in the second transmembrane domain (TM2). 3. Zn2+ inhibited the beta 3 subunit-gated conductance (IC50, 0.31 microM); the inhibition was voltage insensitive. The H292A mutation in beta 3 subunits caused a 1000-fold reduction in Zn2+ potency (IC50, 307 microM). 4. GABA-activated responses recorded from heteromeric alpha 1 beta 3 GABAA receptors were also inhibited by Zn2+ (IC50, 0.11 microM). This inhibition was reduced by mutating H292A in the beta 3 subunit (IC50, 22.8 microM). 5. H292 in TM2 of the beta 3 subunit is an important determinant of a Zn2+ binding site on the GABAA receptor. Its location in the presumed ion channel lining suggests that Zn2+ can penetrate into an anion-selective channel and that the ionic selectivity filter and channel gate are located beyond H292.
Belelli,
The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.
1997, Pubmed,
Xenbase
Belelli,
The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.
1997,
Pubmed
,
Xenbase
Birnir,
A structural determinant of desensitization and allosteric regulation by pentobarbitone of the GABAA receptor.
1997,
Pubmed
Celentano,
Negative modulation of the gamma-aminobutyric acid response by extracellular zinc.
1991,
Pubmed
Connolly,
Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors.
1996,
Pubmed
,
Xenbase
Davies,
Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit.
1997,
Pubmed
Draguhn,
Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+.
1990,
Pubmed
Enz,
A single point mutation decreases picrotoxinin sensitivity of the human GABA receptor rho 1 subunit.
1995,
Pubmed
Frederickson,
Neurobiology of zinc and zinc-containing neurons.
1989,
Pubmed
Gurley,
Point mutations in the M2 region of the alpha, beta, or gamma subunit of the GABAA channel that abolish block by picrotoxin.
1995,
Pubmed
,
Xenbase
Harrison,
Zn2+: an endogenous modulator of ligand- and voltage-gated ion channels.
1994,
Pubmed
Krishek,
Homomeric beta 1 gamma-aminobutyric acid A receptor-ion channels: evaluation of pharmacological and physiological properties.
1996,
Pubmed
,
Xenbase
Ma,
Differential modulation of GABAA receptor-channel complex by polyvalent cations in rat dorsal root ganglion neurons.
1993,
Pubmed
Pan,
Differential modulation by sulfhydryl redox agents and glutathione of GABA- and glycine-evoked currents in rat retinal ganglion cells.
1995,
Pubmed
Smart,
A novel effect of zinc on the lobster muscle GABA receptor.
1982,
Pubmed
Smart,
GABAA receptors are differentially sensitive to zinc: dependence on subunit composition.
1991,
Pubmed
Smart,
A novel modulatory binding site for zinc on the GABAA receptor complex in cultured rat neurones.
1992,
Pubmed
Smart,
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.
1994,
Pubmed
Wang,
A single amino acid in gamma-aminobutyric acid rho 1 receptors affects competitive and noncompetitive components of picrotoxin inhibition.
1995,
Pubmed
,
Xenbase
Wooltorton,
Pharmacological and physiological characterization of murine homomeric beta3 GABA(A) receptors.
1997,
Pubmed
,
Xenbase
Xu,
Interaction of picrotoxin with GABAA receptor channel-lining residues probed in cysteine mutants.
1995,
Pubmed
,
Xenbase
Xu,
Identification of channel-lining residues in the M2 membrane-spanning segment of the GABA(A) receptor alpha1 subunit.
1996,
Pubmed
,
Xenbase
