Simultaneous recordings of action potentials and calcium transients from human induced pluripotent stem cell derived cardiomyocytes

Abstract

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer a unique in vitro platform to study these diseases as they recapitulate many disease phenotypes. The membrane potential (Vm) and intracellular calcium (Ca2+) transient (CaT) are usually investigated separately because incorporating different techniques to acquire both aspects concurrently is challenging. In this study, we recorded Vm and CaT simultaneously to understand the interrelation between these parameters in hiPSC-CMs. For this, we used conventional patch clamp technique to record Vm, and synchronized this with Ca2+ imaging system to acquire CaT from same hiPSC-CMs. Our results revealed that the CaT at 90% decay (CaT90) was longer than AP duration at 90% repolarization (APD90). In addition, there were also strong positive correlation between different parameters of CaT and AP. Majority of delayed after depolarizations (DADs) observed in Vm recording were also characterized by elevations in intracellular Ca2+ level, but in some cases no abnormalities were observed in CaT. However, simultaneous fluctuations in CaT were always observed during early after depolarizations (EADs) in Vm . In summary, simultaneous recording of Vm and CaT broaden the understanding of interrelation between Vm and CaT, and could be used to elucidate mechanism underlying arrhythmia in diseased condition.