(76) THEORETICAL MODEL OF THE MITOCHONDRIAL CA2+-INDUCED CA2+ RELEASE

Vitalii A. Selivanov (1,2), Francois Ichas(1,3) and Jean-Pierre Mazat (1)
(1) Universite Bordeaux 2 and CJF-INSERM 97-05, F-33076 Bordeaux cedex, France
(2) Belozersky Institute, Moscow State University, Moscow, 119899, Russia
(3) Present address: CNR Center for the Study of Biomembranes, Department of Biomedical Sciences, Laboratory of Biophysics and Membrane Biology, University of Padova, Viale G. Colombo 3, I-35121 Padova, Italy

The regulation of the mitochondrial permeability transition (PT), which underlies the mitochondrial Ca2+-induced Ca2+ release (mCICR), is analyzed with a kinetic model. The model describes the evolution of outside and matrix [Ca2+], transmembrane potential? matrix [H+], the relative amount of opened channels responsible for unselective mitochondrial membrane permeability, matrix concentration of the substrate and product of the respiratory chain, matrix [K+]. The model accounts for the following fluxes across the inner mitochondrial membrane: Ca2+ flux through the ruthenium red-sensitive mitochondrial Ca2+ uniporter, H+ transport connected with respiration, consumption of the respiration substrate and its transport within the matrix by the dicarboxilate carrier of, electroneutral passage of the protonated substrate through the membrane by means of dicarboxilate and orthophosphate carriers, leaks of various ions through the membrane during the PT. It is shown, that the hypothesis of the PT regulation by matrix pH allows to describe qualitatively the experimental evolution observed for outside and matrix [Ca2+], transmembrane potential, matrix [H+] and mitochndrial volume. The changes in mitochondrial volume (shrinkage or swelling) are also analyzed.