Selective modulation of NMDA responses by reduction and oxidation.
Electrophysiological responses to the glutamate analog N-methyl-D-aspartate (NMDA) measured in three different central neuronal preparations are subject to a novel modulatory mechanism: they are substantially potentiated after exposure to the disulfide reducing agent dithiothreitol, while oxidation with 5-5-dithiobis-2-nitrobenzoic acid decreases the magnitude of the response. Modification of the NMDA response by either oxidation or reduction does not appear to affect the pharmacological properties of the receptor-channel complex. Since we observe that the redox state of the native receptor-channel complex varies widely among neurons, an in vivo mechanism that can strongly regulate NMDA-activated functions by either reduction or oxidation may exist. In addition, these results suggest that it may be possible to design specific redox agents for characterizing the NMDA receptor-channel complex.
Aizenman
E
E
Department of Neurology Research, Children's Hospital, Boston, Massachusetts 02115.
Lipton
S A
SA
Loring
R H
RH
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D002645:Chickens; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005333:Fetus; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D012160:Retina / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
D001224:Aspartic Acid; D016202:N-Methylaspartate; D004228:Dithionitrobenzoic Acid; D015032:Zinc; D004229:Dithiothreitol