Ventricular cells in fetal guinea pigs have higher anaerobic glycolytic capacity and lower activities of mitochondrial enzymes. In general, embryonic ventricular cells contain approximately 10 times more glyocogen than adult ventricular cells. Although embryonic ventricular cells consume more energy for growth and differentiation, they also utilize contractile proteins that consume less energy than adult ventricular cells. Also, it has been reported that several glycolytic enzyme activities are different between embryonic and adult ventricular cells. As such, the neonatal ventricular cells can maintain the ATP concentration longer than the adult ventricular cells in hypoxic condition; ATP concentration was decreased by 44% in adult rabbit ventricular tissues and 18% in neonatal rabbit ventricular tissues after perfusion of the heart to hypoxic condition (Jarmakani et al., 1978). Although high glycogen content is considered as a cause for the fetal ventricular cells to retain ATP concentration under hypoxic condition, role of the developmental changes in activities of several glycolytic enzymes in ATP production of fetal ventricular cells remain uncertain. We have previously modeled developmental changes in action potentials of rodent ventricular cells (Itoh et al., 2007) on the basis a guinea pig ventricular cell model (Kuzumoto et al., 2008). The quantitative changes in individual ionic components on both cellular membrane and sarcoplasmic reticulum were represented as relative current densities, which were computed from current-voltage curves of the specific ionic components in rodent ventricular cells. Here, we further modified the model to represent the developmental changes in energy metabolism of ventricular cells by implementing glycolytic pathway from glycogen to lactate (Lambeth et al., 2002), and hexokinase kinetics (Lueck et al., 1974), both of which were reported in rodent skeletal muscles. The developmental changes in enzymatic activities were presented as the activities relative to those in the adult ventricular cells, and implemented accordingly to the model to represent specific stages in development. We then simulated effects of hypoxic condition to dynamic changes in contractile force and ATP concentration using the modified model. As a result, the developmental changes in concentrations of intermediate metabolites in glycolytic pathway were well represented in the simulation. Also, we showed that the fetal ventricular cells maintained ATP for longer periods of time than the adult cells, which is consistent with the reported dynamics of the changes under hypoxic condition. On the basis of the simulation, we showed that developmental changes in enzymatic activities of several glycolytic enzymes play important role in maintenance of intracellular ATP concentration under hypoxic condition.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD100
Poster Communications: Simulation of developmental changes in energy metabolism between fetal and adult ventricular cells
T. Toki1,2, H. I. Sano1,3, C. Okubo1,3, Y. Naito1,3, M. Tomita1,3
1. Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan. 2. Department of Policy Management, Keio University, Fujisawa, Japan. 3. Department of Environment and Information Studies, Keio University, Fujisawa, Japan.
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