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

摘要

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 (INa) and funny current (If) made large contributions to a wide range of basic cycle lengths. In all three models, the increase in inward rectifier current (IK1) before the disappearance of If was predicted to result in abnormally high intracellular Ca²⁺ concentrations. Thus, we demonstrated that the developmental changes in APs were well represented, as INa increased before the disappearance of If, followed by a 10-fold increase in IK1.Electronic supplementary materialThe online version of this article (doi:10.1007/s12576-013-0271-x) contains supplementary material, which is available to authorized users.