Decreased NO production during brain cortex mitochondrial permeability transition.

BUSTAMANTE, J.; CZERNICZYNIEC, A.; LORES-ARNAIZ, S.

Jaipur, India

Congreso; International Conference on “Free Radical & Natural Products in Health” & Seventh Annual Meeting of the Society for Free Radical Research; 2008

Society for Free Radical Research International

In this work, the mitochondrial endogenous NO production was evaluated during Ca2+ and alamethicin-induced swelling. Respiratory function and membrane potential were also determined in mouse brain cortex mitochondria. Energized organelles showed partial swelling in the presence of Ca2+ concentrations from 90-200 mM which was complete after addition of alamethicin. Mitochondrial endogenous nitric oxide production was 51% and 73% decreased after 3 and 7 min of  Ca2+ addition and 93% decreased after 1 min of alamethicin induced swelling, as compared with maximal NO levels produced after 1 min of Ca2+ incubation. Ca2+-induced swelling was associated with 38% of mitochondrial depolarization and an impaired respiratory function with a 47% increase in state 4 respiratory rate. Alamethicin induced swelling was accompanied by a 113% increase in state 4 repiratory rate and a 66% decrease in state 3 respiration. L-NNA alone did not induce MPT per se, and reduced NO production by 75%, however 2 min L-NNA pretreatment before Ca2+ addition was able to induce a slight hiperpolarization, without  swelling. We can conclude that during Ca2+ and alamethicin induced MPT in brain cortex mitochondria a decreased mitochondrial endogenous NO production, impaired respiratory function, and a decreased trans-membrane potential, were observed, suggesting that NO should be implicated in the regulation of mitochondrial integrity and physiology.