From ionic to cellular variability in human atrial myocytes: an integrative computational and experimental study

Variability refers to differences in physiological function between individuals, which may translate into different disease susceptibility and treatment efficacy. Experiments in human cardiomyocytes face wide variability and restricted tissue access; under these conditions computational models are a useful complementary tool. We conducted a computational and experimental investigation in cardiomyocytes isolated from samples of the right atrial appendage of patients undergoing cardiac surgery to evaluate the impact of variability in action potentials (APs) and sub-cellular ionic densities on calcium transient dynamics. Results show that: (1) Variability in APs and ionic densities is large, even within an apparently homogenous patient cohort, and translates into {plus minus}100% variation in ionic conductances; (2) Experimentally-calibrated populations of models with wide variations in ionic densities yield APs overlapping with those obtained experimentally, even if AP characteristics of the original generi...