Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex

Neuron. 1992 Jun;8(6):1087-99. doi: 10.1016/0896-6273(92)90130-6.


Nitric oxide (NO) is an important messenger both systemically and in the CNS. In digital Ca2+ imaging and patch-clamp experiments, clinically available nitroso compounds that generate NO are shown to inhibit responses mediated by the NMDA subtype of the glutamate receptor on rat cortical neurons in vitro. A mechanism of action for this effect was investigated by using the specific NO-generating agent S-nitrosocysteine. We propose that free sulfhydryl groups on the NMDA receptor-channel complex react to form one or more S-nitrosothiols in the presence of NO. If vicinal thiol groups react in this manner, they can form a disulfide bond(s), which is thought to constitute the redox modulatory site of the receptor, resulting in a relatively persistent blockade of NMDA responses. These reactions with NO can afford protection from NMDA receptor-mediated neurotoxicity. Our results demonstrate a new pathway for NO regulation of physiological function that is not via cGMP, but instead involves reactions with membrane-bound thiol groups on the NMDA receptor-channel complex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkylating Agents / pharmacology
  • Animals
  • Calcium / metabolism
  • Electrophysiology
  • Intracellular Membranes / metabolism
  • Ion Channels / metabolism*
  • Kainic Acid / pharmacology
  • N-Methylaspartate / pharmacology
  • Neurons / drug effects
  • Neurons / physiology
  • Nitric Oxide / metabolism*
  • Nitroso Compounds / pharmacology
  • Oxidation-Reduction
  • Potassium / pharmacology
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Alkylating Agents
  • Ion Channels
  • Nitroso Compounds
  • Receptors, N-Methyl-D-Aspartate
  • Nitric Oxide
  • N-Methylaspartate
  • Potassium
  • Kainic Acid
  • Calcium