Functional activity and morphology of isolated rat cardiac mitochondria under calcium overload. Effect of naringin.

Abstract

The function of mitochondria as a regulator of myocyte calcium homeostasis has been extensively discussed. The aim of the present work was further clarification of the details of modulation of the functional activity of rat cardiac mitochondria by exogenous Ca²⁺ ions either in the absence or in the presence of the plant flavonoid naringin. Low free Ca²⁺ concentrations (40-250 nM) effectively inhibited the respiratory activity of heart mitochondria, remaining unaffected the efficacy of oxygen consumption. In the presence of high exogenous Ca²⁺ ion concentrations (Ca²⁺ free was 550 µM), we observed a dramatic increase in mitochondrial heterogeneity in size and electron density, which was related to calcium-induced opening of the mitochondrial permeability transition pores (MPTP) and membrane depolarization (Ca²⁺free ions were from 150 to 750 µM). Naringin partially prevented Ca²⁺-induced cardiac mitochondrial morphological transformations (200 µM) and dose-dependently inhibited the respiratory activity of mitochondria (10-75 µM) in the absence or in the presence of calcium ions. Our data suggest that naringin (75 µM) promoted membrane potential dissipation, diminishing the potential-dependent accumulation of calcium ions by mitochondria and inhibiting calcium-induced MPTP formation. The modulating effect of the flavonoid on Ca²⁺-induced mitochondria alterations may be attributed to the weak-acidic nature of the flavonoid and its protonophoric/ionophoric properties. Our results show that the sensitivity of rat heart mitochondria to Ca²⁺ ions was much lower in the case of MPTP opening and much higher in the case of respiration inhibition as compared to liver mitochondria.