Glycine-independent and subunit-specific potentiation of NMDA responses by extracellular Mg2+.
Extracellular Mg2+, which blocks NMDA channels in a voltage-dependent manner and increases the receptor's affinity for glycine, is shown here to potentiate NMDA responses at saturating glycine concentrations. This potentiation, induced by millimolar concentrations of Mg2+, is not mimicked by Ca2+ and Ba2+ and is voltage independent. The potentiation is variable in native receptors of cultured mouse central neurons; in recombinant receptors, it is "permitted" by the NR2B subunit and prevented by the NR1 splice variant containing an N-terminal insert. Mg2+ also induces a shift of the pH sensitivity of NMDA receptors. The similarity and nonadditivity of the effects of Mg2+ and spermine suggest that Mg2+ may be the physiological agonist acting at the subunit-specific spermine site.
Paoletti
P
P
Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France.
Neyton
J
J
Ascher
P
P
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D004357:Drug Synergism; D004553:Electric Conductivity; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005260:Female; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009865:Oocytes / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology; D014981:Xenopus
D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D001464:Barium; D013096:Spermine; D016202:N-Methylaspartate; D008274:Magnesium; D002118:Calcium; D005998:Glycine