Nitric oxide mediates glutamate-induced mitochondrial depolarization in rat cortical neurons

Mitochondria have been considered to be a target for glutamate neurotoxicity. The aim of the present work was to investigate the mechanisms leading to glutamate-mediated mitochondrial deenergization, as measured by mitochondrial membrane potential and cell respiration in cultured neurons. Glutamate exposure to cells induced pronounced mitochondrial depolarization associated with an impairment in neuronal respiration, leading to neuronal ATP depletion. These effects were prevented by both the nitric oxide (. NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester and by the N-methyl-d-aspartate glutamate-subtype receptor inhibitor d-(-)-2-amino-5-phosphopentanoate. Our results suggest that glutamate causes ATP depletion by collapsing mitochondrial membrane potential through a.NO-mediated mechanism.