Current Clamp of Stem Cell Derived Cardiomyocytes on Qpatch

The U.S. Food and Drug Administration (FDA) guidelines S7B mandate the measurement of inhibition of the human ether-a-go-go-related (hERG) ion channel by new drug candidates as it has been found that drug inhibition of the hERG channel can be associated with cardiac action potential (AP) prolongation and lethal cardiac arrhythmias. However, hERG is only one of multiple ion channels involved in forming the cardiac AP and therefore direct measurement of the cardiac AP has the potential to detect the effects of the candidate drug on multiple ion channels potentially affected. Stem cell-derived cardiomyocytes (SC-CM) or induced pluripotent stem cells (iPS-CM) have many of the phenotypic properties of authentic cardiomyocytes e.g. realistic ventricular action potentials. In this work we show how the QPatch can trigger action potentials using rapid switching from voltage to current clamp during recordings on the iPS-CM. We demonstrate that the current clamp recordings made on this automated patch clamp device are comparable to results obtained on standard manual patch clamp rigs. The integrated low volume glass flow channels of the QPatch minimize the consumption of iPS-CM cells - a valuable and often limiting "consumable". Parallel recordings from up to 48 iPS-CM were made on the QPatch HT with full analysis of action potential parameters including action potential duration and upstroke velocity. We measured assay success rates, the stability of action potentials and pharmacological profiles of reference compounds. Current clamp measurements of these cardiomyocytes offer important information to the understanding of the complex pharmacological effect of compounds on ion channels involved in the AP. Our data presented here clearly demonstrate how automated patch clamp on QPatch can augment the throughput of current clamp to meet new demands in drug discovery.