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.
Multiple structural elements determine subunit specificity of Mg2+ block in NMDA receptor channels.
Kuner T, Schoepfer R.
???displayArticle.abstract???
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
