Modeling and simulation of developmental changes in contractile apparatus of ventricular cells

During development, ventricular cells utilize different isoforms of both myosin heavy chain (MHC) and troponin I. The differences in these isoforms affect Ca2+ sensitivity, ATPase activity, and velocity of contraction. In order to consider the differences in isoforms, we integrated a new contraction model with the Kyoto model. Briefly, the new model considered tropomyosin, which inhibits formation of a cross-bridge between actin and myosin filaments. We varied the level of Ca2+ sensitivity in order to obtain similar traces for contractile force between the original Kyoto model and the modified model. We also modified the new contraction model to consider ATP consumption by myosin-ATPase in order to simulate the changes in ATPase activity caused by the difference in MHC isoforms. The modified model enabled us to compare the contribution of developmental changes in ATP consumption via contraction to excitation-contraction coupling, which is regulated differently in fetal and adult guinea pigs.