Nitric oxide mediates glutamate induced mitochondrial depolarization in rat cortical neurons

Mitochondria have been considered to be a target for glutamate neurotoxicit y. The aim of the present work was to investigate the mechanisms leading to glutamate-mediated mitochondrial deenergization, as measured by mitochondr ial membrane potential and cell respiration in cultured neurons. Glutamate exposure to cells induced pronounced mitochondrial depolarization associate d with an impairment in neuronal respiration, leading to neuronal ATP deple tion. These effects were prevented by both the nitric oxide ((NO)-N-.) synt hase inhibitor N-omega-nitro-L-arginine methyl ester and by the N-methyl-D- aspartate glutamate-subtype receptor inhibitor D-(-)-2amino-5-phosphopentan oate Our results suggest that glutamate causes ATP depletion by collapsing mitochondrial membrane potential through a (NO)-N-.-mediated mechanism. (C) 1999 Elsevier Science B.V. All rights reserved.