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 Neurophysiol
2008 Jan 01;991:122-32. doi: 10.1152/jn.01044.2006.
Show Gene links
Show Anatomy links
Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons.
Tong G
,
Takahashi H
,
Tu S
,
Shin Y
,
Talantova M
,
Zago W
,
Xia P
,
Nie Z
,
Goetz T
,
Zhang D
,
Lipton SA
,
Nakanishi N
.
???displayArticle.abstract???
Expression of the NR3A subunit with NR1/NR2 in Xenopus oocytes or mammalian cell lines leads to a reduction in N-methyl-d-aspartate (NMDA)-induced currents and decreased Mg(2+) sensitivity and Ca(2+) permeability compared with NR1/NR2 receptors. Consistent with these findings, neurons from NR3A knockout (KO) mice exhibit enhanced NMDA-induced currents. Recombinant NR3A can also form excitatory glycine receptors with NR1 in the absence of NR2. However, the effects of NR3A on channel properties in neurons and synaptic transmission have not been fully elucidated. To study physiological roles of NR3A subunits, we generated NR3A transgenic (Tg) mice. Cultured NR3A Tg neurons exhibited two populations of NMDA receptor (NMDAR) channels, reduced Mg(2+) sensitivity, and decreased Ca(2+) permeability in response to NMDA/glycine, but glycine alone did not elicit excitatory currents. In addition, NMDAR-mediated excitatory postsynaptic currents (EPSCs) in NR3A Tg hippocampal slices showed reduced Mg(2+) sensitivity, consistent with the notion that NR3A subunits incorporated into synaptic NMDARs. To study the function of endogenous NR3A subunits, we compared NMDAR-mediated EPSCs in NR3A KO and WT control mice. In NR3A KO mice, the ratio of the amplitudes of the NMDAR-mediated component to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated component of the EPSC was significantly larger than that seen in WT littermates. This result suggests that NR3A subunits contributed to the NMDAR-mediated component of the EPSC in WT mice. Taken together, these results show that NR3A subunits contribute to NMDAR responses from both synaptic and extrasynaptic receptors, likely composed of NR1, NR2, and NR3 subunits.
Al-Hallaq,
Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2 subunits.
2002, Pubmed
Al-Hallaq,
Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2 subunits.
2002,
Pubmed
Andersson,
Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B.
2001,
Pubmed
Anson,
Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors.
1998,
Pubmed
Bliss,
A synaptic model of memory: long-term potentiation in the hippocampus.
1993,
Pubmed
Brody,
A developmental influence of the N-methyl-D-aspartate receptor NR3A subunit on prepulse inhibition of startle.
2005,
Pubmed
Chatterton,
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits.
2002,
Pubmed
,
Xenbase
Ciabarra,
Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family.
1995,
Pubmed
,
Xenbase
Cull-Candy,
NMDA receptor subunits: diversity, development and disease.
2001,
Pubmed
Das,
Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A.
1998,
Pubmed
,
Xenbase
Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed
Fukaya,
Retention of NMDA receptor NR2 subunits in the lumen of endoplasmic reticulum in targeted NR1 knockout mice.
2003,
Pubmed
Geyer,
Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.
2001,
Pubmed
Götz,
Functional properties of AMPA and NMDA receptors expressed in identified types of basal ganglia neurons.
1997,
Pubmed
Hirai,
The glycine binding site of the N-methyl-D-aspartate receptor subunit NR1: identification of novel determinants of co-agonist potentiation in the extracellular M3-M4 loop region.
1996,
Pubmed
Hollmann,
Cloned glutamate receptors.
1994,
Pubmed
Kew,
Developmental changes in NMDA receptor glycine affinity and ifenprodil sensitivity reveal three distinct populations of NMDA receptors in individual rat cortical neurons.
1998,
Pubmed
Kirson,
Unique properties of NMDA receptors enhance synaptic excitation of radiatum giant cells in rat hippocampus.
2000,
Pubmed
Kirson,
Early postnatal switch in magnesium sensitivity of NMDA receptors in rat CA1 pyramidal cells.
1999,
Pubmed
Krestel,
A GFP-equipped bidirectional expression module well suited for monitoring tetracycline-regulated gene expression in mouse.
2001,
Pubmed
Kuryatov,
Mutational analysis of the glycine-binding site of the NMDA receptor: structural similarity with bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase
Laube,
Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit.
1997,
Pubmed
Lester,
Interactions between the glycine and glutamate binding sites of the NMDA receptor.
1993,
Pubmed
Lipton,
Excitatory amino acids as a final common pathway for neurologic disorders.
1994,
Pubmed
Malenka,
Long-term potentiation--a decade of progress?
1999,
Pubmed
Mansuy,
Inducible and reversible gene expression with the rtTA system for the study of memory.
1998,
Pubmed
Matsuda,
Specific assembly with the NMDA receptor 3B subunit controls surface expression and calcium permeability of NMDA receptors.
2003,
Pubmed
Matsuda,
Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability.
2002,
Pubmed
Mayer,
Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones.
1987,
Pubmed
McIlhinney,
Assembly intracellular targeting and cell surface expression of the human N-methyl-D-aspartate receptor subunits NR1a and NR2A in transfected cells.
1998,
Pubmed
Nishi,
Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner.
2001,
Pubmed
Paudice,
Evidence for functional native NMDA receptors activated by glycine or D-serine alone in the absence of glutamatergic coagonist.
1998,
Pubmed
Perez-Otano,
Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors.
2001,
Pubmed
Pérez-Otaño,
Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1.
2006,
Pubmed
Rothman,
Excitotoxicity and the NMDA receptor--still lethal after eight years.
1995,
Pubmed
Rumbaugh,
Distinct synaptic and extrasynaptic NMDA receptors in developing cerebellar granule neurons.
1999,
Pubmed
Sasaki,
Characterization and comparison of the NR3A subunit of the NMDA receptor in recombinant systems and primary cortical neurons.
2002,
Pubmed
,
Xenbase
Skeberdis,
Protein kinase A regulates calcium permeability of NMDA receptors.
2006,
Pubmed
Smothers,
Pharmacological characterization of glycine-activated currents in HEK 293 cells expressing N-methyl-D-aspartate NR1 and NR3 subunits.
2007,
Pubmed
Standley,
PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants.
2000,
Pubmed
Sucher,
Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain.
1995,
Pubmed
,
Xenbase
Tong,
Multivesicular release from excitatory synapses of cultured hippocampal neurons.
1994,
Pubmed
Tong,
Block of glutamate transporters potentiates postsynaptic excitation.
1994,
Pubmed
Tovar,
The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro.
1999,
Pubmed
Villmann,
Investigation by ion channel domain transplantation of rat glutamate receptor subunits, orphan receptors and a putative NMDA receptor subunit.
1999,
Pubmed
,
Xenbase
Wong,
Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain.
2002,
Pubmed
Yao,
Characterization of a soluble ligand binding domain of the NMDA receptor regulatory subunit NR3A.
2006,
Pubmed
