Despite extensive preclinical testing, cardiotoxicity remains a common reason for drug candidate failure. Most in vitro assays assess either membrane voltage or calcium dynamics independently, limiting the ability to detect subtle or compound-specific electrophysiological effects. To address this, we developed a high-throughput assay for the simultaneous measurement of membrane potential and intracellular calcium in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using the automated VOLTA Scanner with the voltage-sensitive dye BeRST and a calcium indicator, we record high-resolution (up to 10,000 Hz) action potential waveforms and calcium transients from the same wells before and after compound addition. This multiplexed approach improves the detection of drug-induced changes on ion channel function and supports more comprehensive, scalable cardiotoxicity screening. Multiple assay strategies will be presented.
Vargas et al. (Sun,) studied this question.