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Multiple structural elements determine subunit specificity of Mg2+ block in NMDA receptor channels.
Kuner T
,
Schoepfer R
.
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In NMDA receptor channels, subtype-specific differences of Mg2+ block are determined by the NR2 subunits. Channels assembled from the NR1-NR2A or NR1-NR2B subunits are blocked more strongly than channels formed by the NR1-NR2C or NR1-NR2D subunits, predominantly reflecting a difference in voltage dependence. A determinant of Mg2+ block common to the NR2 subunits is located in the M2 domain (N-site or Q/R/N-site). However, subunit-specific differences of block suggested that additional structural elements exist. Chimeric NR2 subunits were constructed by replacing segments of the least sensitive NR2C subunit with homologous segments of the most sensitive NR2B subunit. Mutant NR2 subunits were coexpressed with wild-type NR1 in Xenopus oocytes, and Mg2+ block was quantified. Replacement of the entire M1-M4 region resulted in a chimera with a sensitivity of Mg2+ block similar to that of the NR2B wild type. Replacing smaller segments or introducing point mutations did not generate channels with Mg2+ block characteristic of NR2B wild type. However, combining in a single chimera three small segments (M1, M2-M3 linker, M4), each independently mediating an increase in Mg2+ block, produced channels close to NR2B wild type. Thus, differences in Mg2+ block as controlled by the NR2 subunits cannot be explained by a single structural determinant in addition to the N-site. Moreover, three elements of the NR2 subunit are the major determinants of subtype-specific differences of Mg2+ block in heteromeric NMDA receptor channels.
Akazawa,
Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats.
1994, Pubmed
Akazawa,
Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats.
1994,
Pubmed
Ascher,
The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture.
1988,
Pubmed
Bennett,
Topology profile for a glutamate receptor: three transmembrane domains and a channel-lining reentrant membrane loop.
1995,
Pubmed
,
Xenbase
Bliss,
A synaptic model of memory: long-term potentiation in the hippocampus.
1993,
Pubmed
Burnashev,
Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor.
1992,
Pubmed
,
Xenbase
Burnashev,
Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes.
1995,
Pubmed
Chen,
Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation.
1992,
Pubmed
Choi,
Glutamate neurotoxicity and diseases of the nervous system.
1988,
Pubmed
Collingridge,
Excitatory amino acid receptors and synaptic plasticity.
1990,
Pubmed
Constantine-Paton,
NMDA receptor as a mediator of activity-dependent synaptogenesis in the developing brain.
1990,
Pubmed
DiFrancesco,
Block and activation of the pace-maker channel in calf purkinje fibres: effects of potassium, caesium and rubidium.
1982,
Pubmed
Ferrer-Montiel,
Molecular design of the N-methyl-D-aspartate receptor binding site for phencyclidine and dizolcipine.
1995,
Pubmed
,
Xenbase
Hollmann,
N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1.
1994,
Pubmed
,
Xenbase
Hollmann,
Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor.
1993,
Pubmed
,
Xenbase
Hollmann,
Cloned glutamate receptors.
1994,
Pubmed
Ikeda,
Cloning and expression of the epsilon 4 subunit of the NMDA receptor channel.
1992,
Pubmed
,
Xenbase
Ishii,
Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits.
1993,
Pubmed
,
Xenbase
Jahr,
A quantitative description of NMDA receptor-channel kinetic behavior.
1990,
Pubmed
Kato,
Developmental changes in the susceptibility to long-term potentiation of neurones in rat visual cortex slices.
1991,
Pubmed
Kato,
Reduced Mg2+ block of N-methyl-D-aspartate receptor-mediated synaptic potentials in developing visual cortex.
1993,
Pubmed
Kawajiri,
Multiple structural determinants of voltage-dependent magnesium block in recombinant NMDA receptors.
1993,
Pubmed
,
Xenbase
Kleckner,
Regulation of hippocampal NMDA receptors by magnesium and glycine during development.
1991,
Pubmed
,
Xenbase
Köhler,
Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing.
1993,
Pubmed
Komuro,
Modulation of neuronal migration by NMDA receptors.
1993,
Pubmed
Kuner,
Ethanol inhibits glutamate-induced currents in heteromeric NMDA receptor subtypes.
1993,
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
Mayer,
Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.
,
Pubmed
Mayer,
Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones.
1987,
Pubmed
McBain,
N-methyl-D-aspartic acid receptor structure and function.
1994,
Pubmed
Meguro,
Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs.
1992,
Pubmed
,
Xenbase
Monyer,
Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.
1994,
Pubmed
Monyer,
Heteromeric NMDA receptors: molecular and functional distinction of subtypes.
1992,
Pubmed
Mori,
Identification by mutagenesis of a Mg(2+)-block site of the NMDA receptor channel.
1992,
Pubmed
,
Xenbase
Moriyoshi,
Molecular cloning and characterization of the rat NMDA receptor.
1991,
Pubmed
,
Xenbase
Nabekura,
Developmental change in voltage dependency of NMDA receptor-mediated response in nucleus tractus solitarii neurons.
1994,
Pubmed
Nowak,
Magnesium gates glutamate-activated channels in mouse central neurones.
,
Pubmed
Sakurada,
Alteration of Ca2+ permeability and sensitivity to Mg2+ and channel blockers by a single amino acid substitution in the N-methyl-D-aspartate receptor.
1993,
Pubmed
,
Xenbase
Sather,
Structural basis of ion channel permeation and selectivity.
1994,
Pubmed
Seeburg,
The NMDA receptor channel: molecular design of a coincidence detector.
1995,
Pubmed
Shatz,
Impulse activity and the patterning of connections during CNS development.
1990,
Pubmed
Stern,
Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors.
1992,
Pubmed
,
Xenbase
Stern-Bach,
Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase
Watanabe,
Developmental changes in distribution of NMDA receptor channel subunit mRNAs.
1992,
Pubmed
Wo,
Transmembrane topology of two kainate receptor subunits revealed by N-glycosylation.
1994,
Pubmed
Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed
Yamazaki,
Cloning, expression and modulation of a mouse NMDA receptor subunit.
1992,
Pubmed
,
Xenbase
