Abstract
We developed a computer model of excitation-contraction (E-C) coupling (Kyoto model: Matsuoka et al., Prog. Biophys. Mol. Biol. 85 (2004) 279), in which mitochondrial oxidative phosphorylation (Korzeniewski & Zoladz, Biophys. Chem. 92 (2001) 17) was incorporated. To further extend the Kyoto model, we improved the mitochondrial energy metabolism by adding pyruvate dehydrogenation, TCA cycle (Cortassa et al., Biophys. J. 84 (2003) 2734), fatty acid β oxidation (Yugi & Tomita, Bioinformatics 20 (2004) 1795) and the reactions of mitochondrial calcium transport (Fall & Keizer, J. theor. Biol. 210 (2001) 151). A kinetic model of the pyruvate dehydrogenase complex was constructed based on experimental kinetic constants. This integrated mitochondria model was developed on the simBio system that was developed to elucidate overall biological process and reproduce dynamic cell functions on computer. In this model, pyruvate dehydrogenase, isocitrate dehydrogenase and oxoglutarate dehydrogenase are activated by Ca2+ increase. Therefore, the ATP production is associated with Ca2+ concentration change. It is demonstrated that the elevation of the cytosolic Ca2+, which accompanied with the stimulated contraction, activates the ATP production. This integrated mitochondria model will provide closer insights into the crosstalk between E-C coupling and energy balance of the cardiac cell. [Jpn J Physiol 55 Suppl:S98 (2005)]
