Brain cortex mitocondrial permeability transition occurs with a decreased mitocondrial endogenous NO production.

BUSTAMANTE, J.; LORES ARNAIZ, S.

Bogotá

Congreso; VI Encuentro Nacional, VII Seminario Internacional de Neurociencias, Universidad Nacional de Colombia; 2008

Mitochondrial endogenous NO production, respiratory function and transmembrane potential were determined in brain mouse cortex mitochondria after Ca2+ and alamethicin induced-swelling. 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 200 mM Ca2+ addition and 93% decreased after 1 min of alamethicin induced swelling, as compared with the NO production by untreated mitochondria. 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 respiratory rate and a 66% decrease in state 3 respiration. L-NNA alone did not induce MPT per se, and reduced NO production by 75%. 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. Similarly, an in vivo hyppocampal mitochondrial observation, in a model of prehepatic portal hypertensive animals showed mitochondrial damage and dysfunction associated with an inhibition of the mtNOS activity and low protein expression. This observation in an in vivo model gives support to the concept that NO decreases during induction of MPT in brain isolated mitochondria due to the decreasing Ca2+ availability occurred as a consequence of the MPT induction.