Abstract Parameter optimization (PO) methods to determine the ionic current composition of experimental cardiac action potential (AP) waveform have been developed using a computer model of cardiac membrane excitation.However, it was suggested that fitting a single AP record in Enhancers the PO method was not always successful in providing a unique answer because of a shortage of information.We found that the PO method worked perfectly if the PO method was applied to a pair of a control AP and a model output AP in which a single ionic current out of six current species, such as I Kr, I CaL, I Na, I Ks, I Kur or I bNSC was partially blocked in silico.When the target was replaced by a pair of experimental control and I Kr-blocked records of APs generated spontaneously in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), the simultaneous fitting of the two waveforms by the PO method was hampered to some extent by the irregular slow fluctuations in the V m recording and/or sporadic alteration in AP configurations in the hiPSC-CMs.This technical problem was largely removed by selecting stable segments of the records for the PO method.
Moreover, the PO method was made fail-proof by running iteratively in identifying the optimized parameter set to reconstruct both the control and the I Kr-blocked AP waveforms.In the lead potential analysis, the quantitative ionic mechanisms deduced from the Bath + Water Toys optimized parameter set were totally consistent with the qualitative view of ionic mechanisms of AP so far described in physiological literature.