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Kinetic and mutational analysis of Zn2+ modulation of recombinant human inhibitory glycine receptors.
Laube B
,
Kuhse J
,
Betz H
.
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1. The effects of Zn2+ on glycine receptor (GlyR) currents were analysed in Xenopus oocytes and human embryonic kidney cells expressing homomeric human wild-type and mutant alpha1 subunit GlyRs. 2. Low concentrations (10 microM) of extracellular Zn2+ converted the partial agonist taurine into a high-efficacy agonist. Concentration-response analysis showed that the EC50 for taurine decreased whereas the Hill coefficient increased under these conditions. In contrast, 50-500 microM Zn2+ showed an increased EC50 value and reduced maximal inducible taurine currents. The potency of competitive antagonists was not affected in the presence of Zn2+. 3. Single-channel recording from outside-out patches revealed different kinetics of glycine- and taurine-gated currents. With both agonists, Zn2+ altered the open probability of the alpha1 GlyR without changing its unitary conductance. Low Zn2+ concentrations (5 microM) increased both the opening frequency and mean burst duration, whereas higher Zn2+ concentrations (> 50 microM) reduced GlyR open probability mainly by decreasing the open frequency and the relative contribution of the longest burst of the single-channel events. 4. Site-directed mutagenesis of the GlyR alpha1 subunit identified aspartate 80 and threonine 112 as important determinants of Zn2+ potentiation and inhibition, respectively, without affecting potentiation by ethanol. 5. Our data support the view that Zn2+ modulates different steps of the receptor binding and gating cycle via specific allosteric high- and low-affinity binding sites in the extracellular N-terminal region of the GlyR alpha1 subunit.
Assaf,
Release of endogenous Zn2+ from brain tissue during activity.
, Pubmed
Assaf,
Release of endogenous Zn2+ from brain tissue during activity.
,
Pubmed
Betz,
Structure and function of inhibitory glycine receptors.
1992,
Pubmed
Bloomenthal,
Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+.
1994,
Pubmed
Bormann,
Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers.
1993,
Pubmed
Chang,
Channel opening locks agonist onto the GABAC receptor.
1999,
Pubmed
Changeux,
Allosteric receptors after 30 years.
1998,
Pubmed
Clements,
Transmitter timecourse in the synaptic cleft: its role in central synaptic function.
1996,
Pubmed
Colquhoun,
Molecular pharmacology. The binding issue.
1993,
Pubmed
Colquhoun,
On the stochastic properties of single ion channels.
1981,
Pubmed
Cuajungco,
Zinc metabolism in the brain: relevance to human neurodegenerative disorders.
1997,
Pubmed
DEL CASTILLO,
Interaction at end-plate receptors between different choline derivatives.
1957,
Pubmed
Danscher,
Exogenous selenium in the brain. A histochemical technique for light and electron microscopical localization of catalytic selenium bonds.
1982,
Pubmed
Fisher,
The role of an alpha subtype M2-M3 His in regulating inhibition of GABAA receptor current by zinc and other divalent cations.
1998,
Pubmed
Flint,
Nonsynaptic glycine receptor activation during early neocortical development.
1998,
Pubmed
Frederickson,
Neurobiology of zinc and zinc-containing neurons.
1989,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Horenstein,
Location of a high affinity Zn2+ binding site in the channel of alpha1beta1 gamma-aminobutyric acidA receptors.
1998,
Pubmed
Kuhse,
Assembly of the inhibitory glycine receptor: identification of amino acid sequence motifs governing subunit stoichiometry.
1993,
Pubmed
,
Xenbase
Langosch,
Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia.
1994,
Pubmed
,
Xenbase
Laube,
Purification and heterologous expression of inhibitory glycine receptors.
1999,
Pubmed
,
Xenbase
Laube,
Hyperekplexia mutations of the glycine receptor unmask the inhibitory subsite for beta-amino-acids.
1995,
Pubmed
,
Xenbase
Laube,
Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit.
1997,
Pubmed
Laube,
Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors.
1995,
Pubmed
,
Xenbase
Lewis,
Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Lynch,
Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways.
1998,
Pubmed
Maksay,
Selective blocking effects of tropisetron and atropine on recombinant glycine receptors.
1999,
Pubmed
,
Xenbase
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Pérez-Clausell,
Intravesicular localization of zinc in rat telencephalic boutons. A histochemical study.
1985,
Pubmed
Rajendra,
Mutation of an arginine residue in the human glycine receptor transforms beta-alanine and taurine from agonists into competitive antagonists.
1995,
Pubmed
Rosenmund,
The tetrameric structure of a glutamate receptor channel.
1998,
Pubmed
Ruiz,
Single cyclic nucleotide-gated channels locked in different ligand-bound states.
1997,
Pubmed
,
Xenbase
Schmieden,
Mutation of glycine receptor subunit creates beta-alanine receptor responsive to GABA.
1993,
Pubmed
,
Xenbase
Schmieden,
A novel domain of the inhibitory glycine receptor determining antagonist efficacies: further evidence for partial agonism resulting from self-inhibition.
1999,
Pubmed
,
Xenbase
Segal,
Rat hippocampal neurons in culture: voltage-clamp analysis of inhibitory synaptic connections.
1984,
Pubmed
Sigworth,
Data transformations for improved display and fitting of single-channel dwell time histograms.
1987,
Pubmed
Smart,
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.
1994,
Pubmed
Smart,
Differential effect of zinc on the vertebrate GABAA-receptor complex.
1990,
Pubmed
Takahashi,
Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels.
1992,
Pubmed
,
Xenbase
Twyman,
Kinetic properties of the glycine receptor main- and sub-conductance states of mouse spinal cord neurones in culture.
1991,
Pubmed
Vallee,
The biochemical basis of zinc physiology.
1993,
Pubmed
Vandenberg,
Distinct agonist- and antagonist-binding sites on the glycine receptor.
1992,
Pubmed
Wang,
A single histidine residue is essential for zinc inhibition of GABA rho 1 receptors.
1995,
Pubmed
,
Xenbase
Wooltorton,
Identification of a Zn2+ binding site on the murine GABAA receptor complex: dependence on the second transmembrane domain of beta subunits.
1997,
Pubmed
,
Xenbase
Ye,
Enhancement of glycine receptor function by ethanol is inversely correlated with molecular volume at position alpha267.
1998,
Pubmed
,
Xenbase
Zarbin,
Glycine receptor: light microscopic autoradiographic localization with [3H]strychnine.
1981,
Pubmed
