Contribution of quantitative changes in individual ionic current systems to the embryonic development of ventricular myocytes: A simulation study

Early embryonic rodent ventricular cells exhibit spontaneous action potential (AP), which disappears in later developmental stages. Here, we used 3 mathematical models - the Kyoto, Ten Tusscher-Panfilov, and Luo-Rudy models - to present an overview of the functional landscape of developmental changes in embryonic ventricular cells. We switched the relative current densities of 9 ionic components in the Kyoto model, and 160 of 512 representative combinations were predicted to result in regular spontaneous APs, in which the quantitative changes in Na⁺ current (I _Na) and funny current (I _f) made large contributions to a wide range of basic cycle lengths. In all three models, the increase in inward rectifier current (I _K1) before the disappearance of I _f was predicted to result in abnormally high intracellular Ca²⁺ concentrations. Thus, we demonstrated that the developmental changes in APs were well represented, as I _Na increased before the disappearance of I _f, followed by a 10-fold increase in I _K1.