Measurements of IK1 currents and paced action potentials in hiPSC derived cardiomyocytes

Measurements of cardiac action potentials (APs) are of special interest for disease modeling, drug discovery and cardiac safety. However, the immature phenotype and heterogeneous ion channel expression of hiPSC-derived cardiomyocytes (CMs), as compared to acutely isolated, primary CMs has limited the physiological relevance of their electrophysiological characterization, in general, and high throughput measurements, in particular. This includes the presence of the pacemaker current I_f (routinely expressed in immature CMs and lost in adult CMs) and reduced densities of hyperpolarizing current I_K1.
However, the maturation of hiPSC-CMs has improved recently, and the paradigm of impaired I_K1 expression in hiPSC-CMs has been challenged. Here, we recorded I_K1 currents and paced action potentials in about 50% of the investigated hiPSC-CMs, using two QPatch assays for automated patch clamp (APC) measurements of “mature” hiPSC CMs in physiological Ringer’s:

1. I_K1 currents
2. Paced action potentials

Both assays run with ~20% success rate (of 48 measurement sites). The increased throughput of action potential measurements compared to manual patch clamp (10 cells per measurement plate) allowed us to measure concentration-response effects of standard compounds such as nifedipine, E4031 and Bay K8644. These measurements were performed in physiological solutions without the use of fluoride or other types of seal-enhancer. Measurements of I_Na, I_Ca and I_Kr from the same cell line have been reported previously.