Prediction of potentially unstable electrical activity during embryonic development of rodent ventricular myocytes

In order to evaluate developmental changes in embryonic ventricular cells at early embryonic (EE) and late embryonic (LE) stage, we aimed to predict potentially unstable action potentials (APs) that could be lethal to developing ventricular cells. Two models of the Kyoto and the Luo-Rudy model were used for simulation of 512 representative combinations by switching the relative activities of 9 ionic components whose activities vary between the EE and LE stages. Out of these 512 combinations in Kyoto model, 144 combinations were predicted potentially unstable resulting from combinations of funny current (I_f), inward rectifier current (I_K1), sustained inward current (I_st), L-type Ca²⁺ current (I_CaL), and Na⁺ current (I_Na). Other 208 and 160 combinations were predicted quiescent membrane potentials and regular spontaneous APs. Based on these results, we suggest that sequential switches of the relative activities of I_Na, I_f, and I_K1 enable cells to avoid unstable patterns.