IDENTIFICATION OF 2 CYSTEINE RESIDUES THAT ARE REQUIRED FOR REDOX MODULATION OF THE NMDA SUBTYPE OF GLUTAMATE-RECEPTOR

Modulation of NMDA-mediated responses by oxidizing and reducing reagen ts has been described in a variety of neuronal preparations. Here, we report that NMDA-gated currents of oocytes expressing heteromeric NMDA receptors are also modulated by sulfhydryl redox reagents. Each cyste ine residue in the NMDAR1 (NR1) subunit and each conserved NMDAR2 (NR2 ) cysteine residue in a prototypical subunit (NR2B) was tested for its role in redox modulation. We have identified 2 cysteines in the NR1 s ubunit that are required for redox modulation of NMDA-gated currents i n oocytes expressing NR1-NR2B, NR1-NR2C, or NR1-NR2D receptors. Mutati on of these same 2 cysteines also eliminated potentiation by spermine and shifted the IC50 for H+ inhibition and the EC(50) for NMDA. Redox modulation of heteromeric NR1-NR(2)A receptors appeared to be differen t from that of the other heteromeric receptors, indicating the presenc e of one or more unique redox modulatory sites on NR1-NR2A receptors.