Heteromeric NMDA receptors: molecular and functional distinction of subtypes.
The N-methyl D-aspartate (NMDA) receptor subtype of glutamate-gated ion channels possesses high calcium permeability and unique voltage-dependent sensitivity to magnesium and is modulated by glycine. Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence. These are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1). Upon expression in cultured cells, the new subunits yielded prominent, typical glutamate- and NMDA-activated currents only when they were in heteromeric configurations with NR1. NR1-NR2A and NR1-NR2C channels differed in gating behavior and magnesium sensitivity. Such heteromeric NMDA receptor subtypes may exist in neurons, since NR1 messenger RNA is synthesized throughout the mature rat brain, while NR2 messenger RNA show a differential distribution.
Monyer
H
H
Center for Molecular Biology, University of Heidelberg, Germany.
Sprengel
R
R
Schoepfer
R
R
Herb
A
A
Higuchi
M
M
Lomeli
H
H
Burnashev
N
N
Sakmann
B
B
Seeburg
P H
PH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D046911:Macromolecular Substances; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D005810:Multigene Family; D016202:N-Methylaspartate / Q000494:pharmacology; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D010455:Peptides; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D005971:Glutamates; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D010455:Peptides; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D018698:Glutamic Acid; D016202:N-Methylaspartate; D004247:DNA; D008274:Magnesium; D005998:Glycine