Population-based mechanistic modeling allows for quantitative predictions of drug responses across cell types

Human adult myocyte and human iPSC-CM responses to perturbations in ion transport pathways. a Action potential (AP) waveforms simulated in human adult myocyte and iPSC-CM mathematical models before (dashed lines) and after (solid lines) 25 and 50% block of IKr. b Calcium transient (CaT) time courses of the two cell types at baseline (dashed lines), and after 25 and 50% block of ICaL (solid lines). c, d Quantification of AP duration at 90% repolarization (APD90, c) and CaT amplitude (CaTA, d) as a function of maximal conductances controlling IKr (GKr, left) and ICaL (GCaL, right) in adult myocyte (blue) and iPSC-CM (red) models. All variables are expressed as a percentage of the control value obtained in the absence of perturbation. e, f Sensitivity coefficients indicating the extent to which perturbations in each ion transport pathway causes changes in APD90 (e) and CaTA (f). Coefficients are shown for both adult myocyte (blue) and iPSC-CM (red) model