Combined Impedance and Extracellular Field Potential Recordings from Human Stem Cell-Derived Cardiomyocytes

Abstract

Measurements of contractility using impedance is a novel method for gaining information about a drug candidate’s potential to disturb cardiac cell contraction. The impedance signal is recorded from a monolayer of cardiac cells, most commonly human induced pluripotent stem cells (hiPSCs), which are becoming an attractive model for safety testing, especially in the light of the Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative introduced in 2013. The goal of this initiative is, in part, to standardize assays, targets and cell types, but also to evaluate the potential of new technologies, in this context, such as impedance. The CardioExcyte 96 is a hybrid system that combines the impedance readout (a measure of cell contractility) with extracellular field potential (EFP) recordings. This chapter focuses on cell handling of hiPSC cardiomyocytes and the short- and long-term investigation into pharmacological effects of a wide range of pharmacological agents, including flecainide, nifedipine, isproterenol and E4031 using the CardioExcyte 96.