Repeated and On-Demand Intracellular Recordings of Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells

Pharmaceutical compounds may have cardiotoxic properties, triggering potentially life-threatening arrhythmias. To investigate proarrhythmic effects of drugs, the patch clamp technique has been used as the gold standard for characterizing the electrophysiology of cardiomyocytes in vitro. However, the applicability of this technology for drug screening is limited, as it is complex to use and features low throughput. Recent studies have demonstrated that 3D-nanostructured electrodes enable to obtain intracellular signals from many cardiomyocytes in parallel; however, the tedious electrode fabrication and limited measurement duration still remain major issues for cardiotoxicity testing. Here, we demonstrate how porous Pt-black electrodes, arranged in high-density microelectrode arrays, can be used to record intracellular-like signals of cardiomyocytes at large scale repeatedly over an extended period of time. The developed technique, which yields highly parallelized electroporations using stimulation voltages around 1 V peak-to-peak amplitude, enabled intracellular-like recordings at high success rates without causing significant alteration in key electrophysiological features. In a proof-of-concept study, we investigated electrophysiological modulations induced by two clinically applied drugs, nifedipine and quinidine. As the obtained results were in good agreement with previously published data, we are confident that the developed technique has the potential to be routinely used in in vitro platforms for cardiotoxicity screening.

Automated summary

The study demonstrates the use of porous Pt-black electrodes arranged in high-density microelectrode arrays to record intracellular-like signals of cardiomyocytes at large scale repeatedly over an extended period of time. This technique enables highly parallelized electroporations using stimulation voltages around 1 V peak-to-peak amplitude, with high success rates and without significant alteration in key electrophysiological features. In a proof-of-concept study, the technique accurately captured electrophysiological modulations induced by two clinically applied drugs, nifedipine and quinidine, showing potential for routine use in in vitro platforms for cardiotoxicity screening.