title: Redox modulation of NMDA receptor-mediated Ca2+ flux in mammalian central neurons.
abstract: NMDA receptor-mediated Ca2+ flux was studied in cultured rat retinal ganglion cells and neocortical neurons. Intracellular free calcium ([Ca2+]i was measured with fura-2 fluorescence imaging. Baseline [Ca2+]i was 59 +/- 5 nM. In low [Mg2+]o, 200 microM NMDA reversibly increased [Ca2+]i to 421 +/- 70 nM. This rise in [Ca2+]i was blocked by the NMDA antagonists APV (200 microM) or [Mg2+]o (1 mM), but only slightly inhibited by the non-NMDA antagonist CNQX (10 microM). Chemical reduction with dithiothreitol (DTT) had no effect on resting [Ca2+]i. However, DTT increased the NMDA-induced rise in [Ca2+]i approximately 1.6-fold; the oxidizing agent dithiobisnitrobenzoic acid (DTNB) reversed this effect. In patch-clamp experiments, DTT increased NMDA-activated whole-cell conductance approximately 1.7-fold in low and high [Ca2+]o. The Ca2+/Na+ permeability ratio of approximately 7 for NMDA channels remained unaltered by chemical reduction. Thus, redox modulation of the NMDA receptor/channel complex results in a dramatic alteration in current magnitude but no change in ionic permeabilities.
authors: Laboratory of Cellular and Molecular Neuroscience, Children's Hospital, Boston, MA.
authors: N J
authors: NJ
authors: Sucher
authors: L A
authors: LA
authors: Wong
authors: S A
authors: SA
authors: Lipton
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D016257:Fura-2; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D004228:Dithionitrobenzoic Acid; D002118:Calcium; D004229:Dithiothreitol; D016257:Fura-2