Electrophysiological Simulation of Developmental Changes in Action Potentials of Cardiomyocytes

Abstract

During cardiomyocyte development, early embryonic ventricular cells show spontaneous activity that disappears at a later stage. Dramatic changes in action potential are mediated by developmental changes in individual ionic currents. Hence, reconstruction of the individual ionic currents into an integrated mathematical model would lead to a better understanding of cardiomyocyte development. To simulate the action potential of the rodent ventricular cell, anecdotally reported developmental changes in individual ionic systems were integrated into two different cardiac electrophysiological models: the Kyoto model and the Luo-Rudy model. Quantitative changes in the ionic currents, pumps, exchangers and sarcoplasmic reticulum Ca2+ kinetics were represented as relative activities, which were multiplied by conductance or conversion factors for individual ionic systems. The integrated models can simulate three representative stages in rodent development: early embryonic, late embryonic and neonatal stages. The simulated action potential of the early embryonic ventricular cell model exhibited spontaneous activity that ceased in the simulated action potential of the late embryonic and neonatal ventricular cell models. The simulations with our models reproduced action potentials consistent with the reported characteristics of the cells in vitro.