Abstract
To clarify complex interactions between cardiac excitation-contraction (E-C) coupling and energy metabolism, a cardiac mitochondria model is developed, which consists of oxidative phosphorylation, TCA cycle, pyruvate metabolism, fatty acid β oxidation, malate shuttle and Ca2+ dynamics. Using this model, we studied regulation of mitochondrial function by Ca2+, and investigated contribution of each functional element of oxidative phosphorylation to mitochondrial oxygen consumption (mVO2), mitochondrial membrane potential and NADH. Calculation of the membrane potential was improved by integrating charge flux across the membrane via proton pumps and transporters. The model simulation revealed that the activation of F1F0-ATPase, adenine nucleotide translocator enhanced mVO2 by about 60%, This result is supported by experimental data demonstrating a large increase in mVO2 of state 3 mitochondria by Ca2+ (Territo et al. Am J Physiol. 278:C423-35, 2000). The expanded computer model, which combines the mitochondria model with an E-C coupling model of cardiomyocyte (Kyoto model), suggested that Ca2+-dependent activation of both oxidative phosphorylation and Ca2+-dependent dehydrogenases plays pivotal roles in regulating cardiac mitochondrial function by stabilizing metabolite concentrations during an increase in workload induced by changing beating frequency. [J Physiol Sci. 2006;56 Suppl:S127]
