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.
Control of NMDA receptor activation by a glycine transporter co-expressed in Xenopus oocytes.
Supplisson S
,
Bergman C
.
???displayArticle.abstract???
We present evidence that membrane transporters can control the membrane receptor's agonist concentration in restricted extracellular spaces of a biological model. The model is constructed by co-expressing glycine/Na/Cl cotransporters (GLYT1b) and NMDA receptors (NMDARs) (composed of the subunits NR1 and NR2A or NR2B) in Xenopus oocytes. We use the high-affinity glycine site of the NMDARs as a sensor of the actual juxtamembrane glycine concentration. We show that glycine uptake by GLYT1b dramatically reduces NMDAR currents by reducing the glycine concentration in extracellular spaces in which diffusion is restricted. This effect appears only in oocytes in which GLYT1b and NMDAR are co-expressed. It is Na+- and voltage-dependent, and is abolished when Na+ is replaced by Li+ and when glycine is replaced by D-serine (a coagonist of the NMDAR that is not transported by GLYT1b). These results demonstrate the ability of the GLYT transporter to reduce glycine concentration at the level of NMDARs in restricted diffusion spaces. This observation could account for a prevalent role of membrane transporters in the modulation of synapse transmission in the CNS. From a more general point of view, our results draw attention to possible significant discrepancies between local concentrations at the level of substrate targets in biological membranes and their concentration in the bulk solution when membrane transporters are present.
Adams,
Gene structure and glial expression of the glycine transporter GlyT1 in embryonic and adult rodents.
1995, Pubmed
Adams,
Gene structure and glial expression of the glycine transporter GlyT1 in embryonic and adult rodents.
1995,
Pubmed
Ascher,
Measuring and controlling the extracellular glycine concentration at the NMDA receptor level.
1990,
Pubmed
Attwell,
Cloners quick on the uptake.
1992,
Pubmed
Attwell,
Nonvesicular release of neurotransmitter.
1993,
Pubmed
Barbour,
Prolonged presence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cells.
1994,
Pubmed
Barry,
Effects of unstirred layers on membrane phenomena.
1984,
Pubmed
Benveniste,
A kinetic analysis of the modulation of N-methyl-D-aspartic acid receptors by glycine in mouse cultured hippocampal neurones.
1990,
Pubmed
Brew,
Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells.
,
Pubmed
Costa,
Improved technique for studying ion channels expressed in Xenopus oocytes, including fast superfusion.
1994,
Pubmed
,
Xenbase
D'Angelo,
Dual-component NMDA receptor currents at a single central synapse.
1990,
Pubmed
Fedele,
[3H]glycine uptake in rat hippocampus: kinetic analysis and autoradiographic localization.
1992,
Pubmed
Guastella,
Cloning, expression, and localization of a rat brain high-affinity glycine transporter.
1992,
Pubmed
,
Xenbase
Johnson,
Glycine potentiates the NMDA response in cultured mouse brain neurons.
,
Pubmed
Kemp,
The glycine site of the NMDA receptor--five years on.
1993,
Pubmed
Kim,
Cloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes.
1994,
Pubmed
Kleckner,
Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes.
1988,
Pubmed
,
Xenbase
Kupper,
Probing the pore region of recombinant N-methyl-D-aspartate channels using external and internal magnesium block.
1996,
Pubmed
,
Xenbase
Kutsuwada,
Molecular diversity of the NMDA receptor channel.
1992,
Pubmed
,
Xenbase
Leonard,
Apparent desensitization of NMDA responses in Xenopus oocytes involves calcium-dependent chloride current.
1990,
Pubmed
,
Xenbase
Li-Smerin,
Effects of intracellular Mg2+ on channel gating and steady-state responses of the NMDA receptor in cultured rat neurons.
1996,
Pubmed
Liu,
Cloning and expression of a spinal cord- and brain-specific glycine transporter with novel structural features.
1993,
Pubmed
,
Xenbase
Luque,
Cellular expression of glycine transporter 2 messenger RNA exclusively in rat hindbrain and spinal cord.
1995,
Pubmed
Mager,
Steady states, charge movements, and rates for a cloned GABA transporter expressed in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Matsui,
Functional comparison of D-serine and glycine in rodents: the effect on cloned NMDA receptors and the extracellular concentration.
1995,
Pubmed
,
Xenbase
Monyer,
Heteromeric NMDA receptors: molecular and functional distinction of subtypes.
1992,
Pubmed
Moriyoshi,
Molecular cloning and characterization of the rat NMDA receptor.
1991,
Pubmed
,
Xenbase
Nicholson,
Interaction between diffusion and Michaelis-Menten uptake of dopamine after iontophoresis in striatum.
1995,
Pubmed
Nowak,
Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg(2+)-free solutions.
1992,
Pubmed
Paoletti,
Glycine-independent and subunit-specific potentiation of NMDA responses by extracellular Mg2+.
1995,
Pubmed
,
Xenbase
Schell,
D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release.
1995,
Pubmed
Schell,
D-serine as a neuromodulator: regional and developmental localizations in rat brain glia resemble NMDA receptors.
1997,
Pubmed
Smith,
Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors.
1992,
Pubmed
Thiels,
In vivo modulation of N-methyl-D-aspartate receptor-dependent long-term potentiation by the glycine modulatory site.
1992,
Pubmed
Thomson,
Glycine enhances NMDA-receptor mediated synaptic potentials in neocortical slices.
1989,
Pubmed
Thomson,
Glycine is a coagonist at the NMDA receptor/channel complex.
1990,
Pubmed
Tong,
Block of glutamate transporters potentiates postsynaptic excitation.
1994,
Pubmed
Tsuzuki,
Ion permeation properties of the cloned mouse epsilon 2/zeta 1 NMDA receptor channel.
1994,
Pubmed
,
Xenbase
Westergren,
Concentrations of amino acids in extracellular fluid after opening of the blood-brain barrier by intracarotid infusion of protamine sulfate.
1994,
Pubmed
Wilcox,
Glycine regulation of synaptic NMDA receptors in hippocampal neurons.
1996,
Pubmed
Wolf,
Isolation, physicochemical properties, and the macromolecular composition of the vitelline and fertilization envelopes from Xenopus laevis eggs.
1976,
Pubmed
,
Xenbase
Zafra,
Glycine transporters are differentially expressed among CNS cells.
1995,
Pubmed
Zampighi,
A method for determining the unitary functional capacity of cloned channels and transporters expressed in Xenopus laevis oocytes.
1995,
Pubmed
,
Xenbase
