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

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer a unique in vitro platform to study cardiac diseases, as they recapitulate many disease phenotypes. The membrane potential (V_m) 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 V_m and CaT simultaneously to understand the interrelation between these parameters in hiPSC-CMs. For this, we used a conventional patch clamp technique to record V_m, and synchronized this with a Ca²⁺ imaging system to acquire CaT from same hiPSC-CMs. Our results revealed that the CaT at 90% decay (CaT90) was longer than action potential (AP) duration at 90% repolarization (APD90). In addition, there was also a strong positive correlation between the different parameters of CaT and AP. The majority of delayed after depolarizations (DADs) observed in the V_m recording were also characterized by elevations in the 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 V_m In summary, simultaneous recording of V_m and CaT broadens the understanding of the interrelation between V_m and CaT and could be used to elucidate the mechanisms underlying arrhythmia in cardiac disease condition.