Establishment of an automated patch-clamp platform for electrophysiological and pharmacological evaluation of hiPSC-CMs

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have evolved into widely used and reliable cell sources for modeling cardiovascular channelopathies and for drug safety pharmacology. However, the electrophysiological and pharmacological applications of hiPSC-CMs are hampered by manual patch-clamp technique, which is labor-intensive and generates low output. The automated patch-clamp technique is showing potential to overcome this problem. Here, we describe a new dissociation method, with which we can harvest a vast number of single relaxed hiPSC-CMs with smooth membrane suited for automated patch-clamp. Using the automated whole-cell patch-clamp technology, we report a high success rate for cell capture and whole-cell access (around 70%). We are able to identify and record several currents and paced action potentials (APs) with different success rates, including Na⁺ current (I_Na), L-type Ca²⁺ current (I_CaL), two specific K⁺ currents, the transient outward K⁺ current (I_to) and the inward rectifier K⁺ current (I_K1). Moreover, we successfully applied dynamic current-clamp to virtually increase I_K1 for AP recordings. Our study suggests that automated patch-clamp technology could be used to investigate the relevant ionic currents and APs in hiPSC-CMs. The combination of automated patch-clamp and hiPSC-CM technologies promises a wide range of applications in the future.