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 her e to potentiate NMDA responses at saturating glycine concentrations. T his potentiation, induced by millimolar concentrations of Mg2+, is not mimicked by Ca2+ and Ba2+ and is voltage independent. The potentiatio n is variable in native receptors of cultured mouse central neurons; i n recombinant receptors, it is ''permitted'' by the NR2B subunit and p revented by the NR1 splice variant containing an N-terminal insert. Mg 2+ also induces a shift of the pH sensitivity of NMDA receptors. The s imilarity and nonadditivity of the effects of Mg2+ and spermine sugges t that Mg2+ may be the physiological agonist acting at the subunit-spe cific spermine site.