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

被引:226
作者
SULLIVAN, JM
TRAYNELIS, SF
CHEN, HSV
ESCOBAR, W
HEINEMANN, SF
LIPTON, SA
机构
[1] CHILDRENS HOSP,DEPT NEUROL,MOLEC & CELLULAR NEUROSCI LAB,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115
[3] EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322
关键词
D O I
10.1016/0896-6273(94)90258-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Modulation of NMDA-mediated responses by oxidizing and reducing reagents 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 cysteine 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 subunit that are required for redox modulation of NMDA-gated currents in oocytes expressing NR1-NR2B, NR1-NR2C, or NR1-NR2D receptors. Mutation 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 different from that of the other heteromeric receptors, indicating the presence of one or more unique redox modulatory sites on NR1-NR2A receptors.
引用
收藏
页码:929 / 936
页数:8
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