Glycine-independent and subunit-specific potentiation of NMDA responses by extracellular Mg2+

Neuron. 1995 Nov;15(5):1109-20. doi: 10.1016/0896-6273(95)90099-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Barium / pharmacology
  • Calcium / pharmacology
  • Cell Line
  • Drug Synergism
  • Electric Conductivity
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Female
  • Glycine / metabolism
  • Glycine / pharmacology*
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney
  • Magnesium / pharmacology*
  • Membrane Potentials
  • Mice
  • N-Methylaspartate / pharmacology*
  • Oocytes / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Recombinant Proteins / metabolism
  • Spermine / pharmacology
  • Xenopus


  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Barium
  • Spermine
  • N-Methylaspartate
  • Magnesium
  • Calcium
  • Glycine