Quantitative cross-species translators of cardiac myocyte electrophysiology: model training, experimental validation, and applications

摘要: Animal experimentation is key in the evaluation of cardiac efficacy and safety novel therapeutic compounds. However, inter-species differences mechanisms regulating excitation-contraction coupling can limit translation experimental findings from animal models to human physiology, undermine assessment drugs9 safety. Here, we built a suite translators for quantitatively mapping electrophysiological responses ventricular myocytes across species. We trained these statistical operators using broad dataset obtained by simulating populations our biophysically detailed computational action potential Ca2+ transient mouse, rabbit, human. then tested against data describing response stimuli, such as ion channel block, change beating rate, β-adrenergic challenge. demonstrate that this approach well suited predicting effects perturbations different species or conditions, suggest its integration into mechanistic studies drug development pipelines.