We studied the Са2+- 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 Са2+ or 1 to 50 μM Сd2+ to the medium caused swelling of the mitochondria. With increase in concentrations of Са2+ and Cd2+, the latency of the effect decreased, and the rate of swelling of these organelles increased. Upon isolated action of Са2+, 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 Са2+- 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 Са2+- and Cd2+-induced swelling of the mitochondria, respectively. Cyclosporine A (10 μM) suppressed completely the Са2+-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 Са2+-stimulated process. Therefore, the distinctions between the kinetics of Са2+- 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
K. W. Kinnally, D. Zorov, Y. Antonenko, and S. Perini, “Calcium modulation of mitochondrial inner membrane channel activity,” Biochem. Biophys. Res. Commun., 176, No. 3, 1183–1188 (1991).
I. Szabo and M. Zoratti, “The giant channel of the inner mitochondrial membrane is inhibited by cyclosporin A,” J. Biol. Chem., 266, 3376–3379 (1991).
I. Szabo, P. Bernardi, and M. Zoratti, “Modulation of the mitochondrial megachannel by divalent cations and protons,” J. Biol. Chem., 267, 2940–2946 (1992).
I. Szabo and M. Zoratti, “The mitochondrial megachannel is the permeability transition pore,” J. Bioenerg. Biomembr., 24, No. 1, 111–117 (1992).
I. Szabo and M. Zoratti, “The mitochondrial permeability transition pore may comprise VDAC molecules. I. Binary structure and voltage dependence of the pore,” FEBS Lett., 330, No. 2, 201–205 (1993).
T. E. Gunter and D. R. Pfeiffer, “Mechanisms by which mitochondria transport calcium,” Am. J. Physiol., 258, C755–C786 (1990).
M. Zoratti and I. Szabo, “The mitochondrial permeability transition,” Biochim. Biophys. Acta, 1241, No. 2, 139–176 (1995).
T. E. Gunter, D. I. Yule, K. K. Gunter, et al., “Calcium and mitochondria,” FEBS Lett., 567, 96–102 (2004).
G. Kroemer, L. Galluzzi, and C. Brenner, “Mitochondrial membrane permeabilization in cell death,” Physiol. Rev., 87, 99–163 (2007).
M. Crompton, “Mitochondrial intermembrane junctional complexes and their role in cell death,” J. Physiol., 529, 11–21 (2000).
D. Nicholls and K. Akerman, “Mitochondrial calcium transport,” Biochim. Biophys. Acta, 683, No. 1, 57–88 (1982).
J. O. Jarvisalo, J. Kilpio, and N. E. Saris, “Toxicity of cadmium to renal mitochondria when administered in vivo and in vitro,” Environ. Res., 22, No. 1, 217–233 (1980).
O. V. Akopova and V. F. Sagach, “Induction of the opening of mitochondrial pore upon the action of Са2+ in the rat myocardium,” Ukr. Biokhim. Zh., 76, No. 1, 48–55 (2004).
W.-K. Lee, U. Bork, F. Gholamrezaei, and F. Thévenod, “Cd2+-induced cytochrome C release in apoptotic proximal tubule cells: role of mitochondrial permeability transition pore and Ca2+ uniporter,” Am. J. Physiol. Renal. Physiol., 288, F27–F39 (2005).
R. A. Haworth and D. R. Hunter, “The Ca2+-inducedmembrane transition in mitochondria. II. Nature of the Ca2+ trigger site,” Arch. Biochem. Biophys., 195, No. 2, 460–467 (1979).
S. A. Novgorodov, T. I. Gudz, Y. M. Milgrom, and G. P. Brierley, “The permeability transition in heart mitochondria is regulated synergistically by ADP and cyclosporine A,” J. Biol. Chem., 267, 16274–16282 (1992).
P. Bernardi, P. Veronese, and V. Petronilli, “Modulation of the mitochondrial cyclosporine A-sensitive permeability transition pore. I. Evidence for two separate Me2+ binding sites with opposing effects on the pore open probability,”J. Biol. Chem., 268, 1005–1010 (1993).
G. P. Brierley, R. N. Bhattacharyya, and B. A. Shearman, “Ion transport by heart mitochondria. VII. Activation of the energy-linked accumulation of Mg++ by Zn++ and other cations,” J. Biol. Chem., 242, 1115–1122 (1967).
B. K. Rasheed, J. J. Diwan, and D. R. Sanadi, “Activation of potassium ion transport in mitochondria by cadmium ion,” J. Biochem., 144, No. 3, 643–647 (1984).
E. A. Belyaeva, V. V. Glazunov, E. R. Nikitina, and S. M. Korotkov, “Bivalent metal ions modulate Cd2+ effects on isolated rat liver mitochondria,” J. Bioenerg. Biomembranes, 33, No. 4, 303–318 (2001).
E. A. Belyaeva, V. V. Glazunov, and S. M. Korotkov, “Cyclosporine A-sensitive permeability transition pore is involved in Cd2+-induced dysfunction of isolated rat liver mitochondria: doubts no more,” Arch. Biochem. Biophys., 405, No. 2, 252–264 (2002).
M. R. Duchen, O. McGuinness, L. A. Brown, et al., “On the involvement of a cyclosporine A-sensitive mitochondrial pore in myocardial reperfusion injury,” Cardiovascul. Res., 27, 1790–1794 (1993).
A. Lehninger, The Mitochondrion. Molecular Basis of Structure and Function [Russian translation], Mir, Moscow (1966).
W. C. Schneider and G. H. Hogeboom, “Intracellular distribution of enzymes. Further studies of the distribution of cytochrome C in rat liver homogenates,” J. Biol. Chem., 183, 123–128 (1950).
J. H. Lowry, N. J. Rosenbrough, A. L. Farr, et al., “Protein measurements with Folin protein reagent,” J. Biol. Chem., 193, No. 1, 265–275 (1951).
B. Chance and G. Williams, “Respiratory enzymes in oxidative phosphorylation. Kinetics of oxygen utilization,” J. Biol. Chem., 217, 383–393 (1955).
D. R. Hunter, R. A. Haworth, and J. H. Southard, “Relationship between configuration, function, and permeability in calcium-treated mitochondria,” J. Biol. Chem., 251, 5069–5077 (1976).
L. S. Vovkanych, Effects of Cations of Alkaline-Earth and Transition Metals on Functioning of the Rat Liver Mitochondria [in Ukrainian], Abstr. of Cand. Thesis, Biol. Sci., Kyiv (1999).
T. Keleti, Basic Enzyme Kinetics [Russian translation], Mir, Moscow (1990).
A. Rasola and P. Bernardi, “The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis,” Apoptosis, 12, No. 5, 815–833 (2007).
O. McGuinness, N. Yafei, A. Costi, and M. Crompton, “The presence of two classes of high-affinity cyclosporine A binding sites in mitochondria. Evidence that the minor component is involved in the opening of an inner-membrane Ca2+-dependent pore,” Eur. J. Biochem., 194, No. 2, 671–679 (1990).
D. V. de Macedo, C. da Costa, and L. Pereira-Da-Silva, “The permeability transition pore opening in intact mitochondria and submitochondrial particles,” Comp. Biochem. Physiol. Ser. B (Biochem. Mol. Biol.), 118, No. 1, 209–216 (1997).
E. E. Jacobs, M. Jacob, D. R. Sanadi, and L. B. Bradley, “Uncoupling of oxidative phosphorylation by cadmium ion,” J. Biol. Chem., 223, 147–156 (1956).
M. Crompton, “The mitochondrial permeability transition pore and its role in cell death,” Biochem. J., 34, 233–249 (1999).
G. Kroemer and J. C. Reed, “Mitochondrial control of cell death,” Nat. Med., 6, 513–519 (2000).
L. N. Shapoval, O. V. Dlytrenko, L. S. Pobegailo, et al., “Changes in the mitochondrial permeability in medullary cardiovascular neurons influence the hemodynamics in rats,” Neurophysiology, 39, No. 4/5, 343–346 (2007).
Author information
Authors and Affiliations
Corresponding author
Additional information
*Deceased
Rights and permissions
About this article
Cite this article
Kravens’ka, E.V., Nalyvaiko, N.V., Fedirko, N.V. et al. Kinetic Analysis of the Calcium- and Cadmium-Induced Development of Nonspecific Permeability of the Mitochondrial Inner Membrane. Neurophysiology 40, 252–260 (2008). https://doi.org/10.1007/s11062-009-9045-8
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11062-009-9045-8