Kinetic analysis of the calcium- and cadmium-induced development of nonspecific permeability of the mitochondrial inner membrane

We studied the Ca2+- and Cd2+-induced development of the nonspecific permeability of the mitochondrial inner membrane in preparations obtained from rat liver tissue, which is accompanied by swelling of these organelles and intensification of light dispersion of their suspension. Addition of 5 to 100 μM Ca2+ or 1 to 50 μM Cd2+ to the medium caused swelling of the mitochondria. With increase in concentrations of Ca2+ and Cd2+, the latency of the effect decreased, and the rate of swelling of these organelles increased. Upon isolated action of Cd2+, the intensity of the process (amplitude of changes) did not depend significantly on the concentration of the above ions, while upon isolated action of Cd2+, it was the maximum at the concentration of 1 mM and noticeably decreased with increase in the concentration. The dependence of the rate of Ca2+- and Cd2+-induced swelling of the mitochondria on the concentration of these ions was described by power and sigmoid functions, respectively. The calculated maximum rate and the constant of 50% saturation of these processes were equal to 0.609 and 1.084 extinction units/min·mg protein and 19.85 and 7.28 μM for Ca2+- and Cd2+-induced swelling of the mitochondria, respectively. Cyclosporine A (10 μM) uppressed completely the Ca2+-induced swelling of the mitochondria and decreased only partly the Cd2+-induced swelling. Dithiothreitol (1 mM) inhibited completely the latter effect but did not influence significantly the Ca2+-stimulated process. Therefore, the distinctions between the kinetics of Ca2+- and Cd2+-induced swelling of the mitochondria, as well as the different sensitivity of these processes to cyclosporine A and dithiothreitol, prove that the mechanisms underlying interactions between the cations of the above metals and the inner mitochondrial membrane in the course of the development of nonspecific permeability of these organelles are dissimilar. © 2008 Springer Science+Business Media, Inc.