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 cardiac 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 a conventional patch clamp technique to record Vm, 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 Vm 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 Vm. In summary, simultaneous recording of Vm and CaT broadens the understanding of the interrelation between Vm and CaT and could be used to elucidate the mechanisms underlying arrhythmia in cardiac disease condition.

Keywords

• hiPSC-CMs
• Membrane potential
• Calcium transient
• Delayed after depolarization
• Early after depolarization