Fig. 6.
IsoKs accelerate the rate of the mPT induction but not the order of the reaction. A. Dependence of k1 (the Ca2+ uptake rate) on the presence of IsoKs. B. Dependence of n (the reaction order) on the presence of IsoKs. C. Dependence of k2′ (rate of the mPT induction) on the presence of IsoKs. The kinetic analysis was performed using a recently introduced kinetic model (54). The model functionally resolves possible sites of action for different mPT modulators.
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where [MH-(Ca2+)i]A represents the population of active, unswollen mitochondria ([MH]A), i being the number of Ca2+ already adsorbed by a given mitochondria. Ca2+ uptake occurs during the k1 step shown in scheme as formation of [MH-(Ca2+)i+1]A, and it initiates the mPT process that we describe as a sequence of two steps. The k2 step is rate-limiting step of the mPT induction that results in the formation of the intermediate state [MH]I and depends on the reaction constant k2′. The next step (kp) leads to the formation of a population of inactive (swollen) mitochondria, represented as [MH]N, with all Ca2+ released back to the medium. [Ca2+]out is the concentration of free Ca2+ in the medium, available for absorption by mitochondria. Data were plotted as the mean ± sem, N=3, *, p < 0.05 compare with IsoKs untreated mitochondria.