Redox Sensitivity of NMDA Receptors

  • Stuart A. Lipton
Part of the Methods in Molecular Biology™ book series (MIMB, volume 128)


The redox modulatory sites of the NMDA receptor consist of critical cysteine residues, which when chemically reduced, increase the magnitude of NMDA-evoked responses. In contrast, after oxidation, NMDA-evoked responses are decreased in size. In recent years, as endogenous sources of oxidizing and reducing agents have been discovered, redox modulation of protein function has been recognized to be an important physiologic, as well as pathologic mechanism for many cell types. For our purposes, I will confine this review of redox modulation to covalent modification of sulfhydryl (thiol) groups on protein cysteine residues of native NMDA receptors. Of note, considerable recent work has focused on the use of recombinant NMDA receptor subunits and site-directed mutagenesis to identify the critical cysteine residues involved in this redox modulation, but these recombinant methods will not be reviewed here. For a recent summary of the molecular data, see ref. 1. If the cysteine sulfhydryls possess a sufficient redox potential, oxidizing agents can react to form adducts on single thiol groups, or if two free sulfhydryl groups are vicinal (in close proximity), disulfide bonds may possibly be formed. Reducing agents can regenerate free sulfhydryl (—SH) groups by donating electron(s). Considering endogenous redox agents, in addition to the usual suspects, including glutathione, lipoic acid, and reactive oxygen species, nitric oxide and its redox-related species have recently come to the fore.


NMDA Receptor Lipoic Acid Redox Modulation NMDA Receptor Subunit Redox Site 
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Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  • Stuart A. Lipton
    • 1
  1. 1.CNS Research Institute, Brigham and Women’s HospitalHarvard Medical SchoolBoston

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