Glutamate-mediated inhibition of oxidative phosphorylation in cultured retinal cells

Glutamate is an excitotoxin responsible for causing neuronal damage associa ted with mitochondria dysfunction. We have analyzed the relationship betwee n the mitochondrial respiratory rate, the membrane potential (Delta Psi) an d the activity of mitochondrial complexes in retinal cells in culture, used as neuronal models. Glutamate (10 mu M-10 mM) dose-dependently decreased t he O-2 consumption and the membrane potential. A linear correlation was fou nd between these parameters, suggesting that the mitochondrial respiratory function was affected. Exposure to glutamate (100 mu M) for 10 min, in the absence of Mg2+, inhibited the activity of complex I (26.3%), complexes II/ III (22.2%) and complex IV (26.7%). MK-801 ((+)-5-methyl-10,11-dihydro-5H-d ibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate), a non-competitive ant agonist of the NMDA (N-methyl-D-aspartate) receptors, completely reversed t he effect exerted by 100 mu M glutamate at the level of complexes I, II/III and IV. These results suggest that NMDA receptor-mediated inhibition of mi tochondrial respiratory chain complexes may be responsible for the alterati on in the respiratory rate of chick retinal cells submitted to glutamate. ( C) 2000 Elsevier Science Ltd. All rights reserved.