Abstract
Cardiovascular disease remains the leading global cause of death. Evaluating potential cardiotoxicity continues to be a major challenge and expense in early drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a physiologically relevant and accessible model for in vitro cardiac pharmacology and cardiotoxicity testing.
Cardiac ion channels are key therapeutic targets and central contributors to drug-induced cardiotoxicity, highlighting the importance of electrophysiological studies using hiPSC-CMs. However, conventional manual patch-clamp techniques are labor-intensive and low-throughput, limiting their utility for large-scale screening.
Automated patch clamp (APC) systems enable high-throughput, precise electrophysiological measurements across large hiPSC-CM populations, accelerating screening workflows and lowering costs associated with cardiac pharmacology and safety assessment.
This study evaluates axoCells Ventricular Cardiomyocytes using Sophion’s QPatch and Qube 384 APC platforms to characterize electrophysiological properties and assess their suitability for evaluating cardiac action potentials and preclinical cardiotoxicity screening.
Cardiac voltage-gated currents (Nav and Cav) and action potentials were recorded on QPatch with 40% whole-cell success rates in physiological solution. Pharmacological and biophysical evaluation identified the presence of TTX-resistant Nav1.5 channels and L-type Cav1.2 channels. Qube 384 was used to perform a concentration-response experiment with a known Nav – channel blocker, tetracaine. The assay ran with more than 80% whole-cell success rate and yielded IC50 values in good agreement with reported values for Nav1.5 – channels.
APC recordings on the QPatch platform assessed key metrics including whole-cell success rates, sodium (Nav) and calcium (Cav) currents, and action potentials. Pharmacological profiling confirmed the presence of TTXresistant Nav1.5 currents, inhibition by nifedipine, and potentiation by bay K8644. These findings were reproducible on the Qube 384 platform, supporting the utility of axoCells for scalable cardiac electrophysiology studies. By leveraging the scalability and precision of this APC technology we wish to enable higher-throughput cardiotoxicity testing with greater physiological relevance than the equivalent animal models and heterologous cells, and with easier access and more consistent performance than human primary tissue.
