Cardiomyocytes - "Combining automated patch clamp, impedance and EFP of hiPSC-CMs"
CardioExcyte 96 SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) Patchliner Application Note
Cells kindly provided by Takara-Clonetech.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are gaining interest in cardiac safety screening. Given their recapitulation of native behavior, availability, ease of use and standardized production, they are likely to provide a viable alternative to acutely isolated cardiomyocytes to assess the pro-arrhythmic potentials of drug candidates. In 2013 the Comprehensive In-vitro Proarrhythmia Assay (CiPA) was introduced to provide a more complete assessment of pro- arrythmic risk by evaluating and implementing currently available high throughput methods and evaluating the potential use of hiPSC-CMs as a model system for cardiac safety testing. Until now, drug safety testing has focussed on interaction with the hERG channel and QT prolongation which can lead to potentially fatal torsades de pointes (TdP). Although this approach has been largely successful in preventing new drugs reaching the market with unexpected potential to cause TdP, it is also possible that potentially valuable therapeutics have failed due to this early screening. The CiPA initiative has proposed an expansion of patch clamp assessment beyond hERG to include, e.g. NaV1.5 and CaV1.2. In addition, techniques such as multi-electrode array (MEA) and impedance are being thoroughly evaluated as complementary techniques to patch clamp.
Here we present data recorded using the automated patch clamp platforms, the Patchliner, SyncroPatch 96 and SyncroPatch 384PE on Cellartis® Cardiomyocytes (Takara Bio Europe Cat nr. Y10075). Recordings of NaV1.5 and CaV1.2 are shown. Impedance and EFP recordings were also performed using the CardioExcyte 96, and the effects of verapamil and sotalol are shown.