Permeability transition in brain cortex mitochondria occurs with a decreased production of nitric oxide.

BUSTAMANTE, J.; CZERNICZYNIEC, A.; ARRIAGA, J.; MICUCCI, M.; LORES ARNAIZ, S.

Pinamar, Pcia de Buenos Aires, Argentina

Congreso; X Congreso Panamerican Association for Biochemistry and Molecular Biology, XLI Reunión Annual Sociedad Argentina de Investigación Bioquímica, XX Reunión Anual Sociedad Argentina de Neuroquímica.; 2005

Panamerican Association for Biochemistry and Molecular Biology, Sociedad Argentina de Investigación Bioquímica, Sociedad Argentina de Neuroquímica

Increased and sustained cytosolic Ca2+ concentrations are predominantly coped by mitochondria, which are able to accumulate this cation in high concentrations, in order to permit the signaling function of Ca2+. In this way, mitochondria can protect neurons from deleterious effects of abnormal Ca2i influx, which could lead to the activation of hydrolytic and degradation pathways associated with apoptosis and necrosis. In order to analyze the effect of Ca2+ loading in rat brain cortex mitochondria, permeability transition (MPT), respiratory function and mitochondrial membrane potential, were studied in association with the mitochondrial endogenous NO production. Energized organelles after induced MPT by addition of Ca2+ (200 nmol/mg protein), showed mitochondria depolarization (20%) and impaired respiratory function, with a 60% decrease in state 3 respiratory rate. These findings were accompanied by a 46% decrease in mitochondrial endogenous NO production. L-NNA pretreatment before Ca2+ loading, exerted 31% protection against swelling and did not change mitochondrial NO production. Meanwhile ADP addition shortly before Ca2+ loading, protected against swelling, it did not restore mitochondrial respiration, and did not change NO production as compared with  Ca2+ loaded organelles. We can conclude that Ca2+ MPT in brain cortex mitochondria is associated with an impaired respiratory function, decreased transmembrane potential and a decreased mitochondrial endogenous NO production.