Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes

摘要: Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are increasingly recognized as valuable for determining the effects of drugs on ion channels but they do not always accurately predict contractile responses heart. This is in part attributable to their immaturity sensitivity measurement tools may also be limiting. Measuring action potential, calcium flux or contraction individually misses critical information that captured when interrogating complete excitation-contraction coupling cascade simultaneously. Here, we develop an hypothesis-based statistical algorithm identifies mechanisms action. We design and build a high-speed optical system measure cytosolic simultaneously using fluorescent sensors. These measurements automatically processed, quantified then assessed by algorithm. Multiplexing these three physical features hiPSC-CMs allows identification all major drug classes affecting contractility with detection sensitivities higher than individual contraction.