Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes—An Artifact by Big Conductance Calcium Activated Potassium Current (I<sub>bk,Ca</sub>)
András Horváth,
Torsten Christ,
Jussi T. Koivumäki,
Maksymilian Prondzynski,
Antonia T. L. Zech,
Michael Spohn,
Umber Saleem,
Ingra Mannhardt,
Bärbel Ulmer,
Evaldas Girdauskas,
Christian Meyer,
Arne Hansen,
Thomas Eschenhagen,
Marc D. Lemoine
Affiliations
András Horváth
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Torsten Christ
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Jussi T. Koivumäki
BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
Maksymilian Prondzynski
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Antonia T. L. Zech
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Michael Spohn
Bioinformatics Core, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Umber Saleem
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Ingra Mannhardt
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Bärbel Ulmer
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Evaldas Girdauskas
DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany
Christian Meyer
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, 6721 Szeged, Hungary
Arne Hansen
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Thomas Eschenhagen
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Marc D. Lemoine
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent an unlimited source of human CMs that could be a standard tool in drug research. However, there is concern whether hiPSC-CMs express all cardiac ion channels at physiological level and whether they might express non-cardiac ion channels. In a control hiPSC line, we found large, “noisy” outward K+ currents, when we measured outward potassium currents in isolated hiPSC-CMs. Currents were sensitive to iberiotoxin, the selective blocker of big conductance Ca2+-activated K+ current (IBK,Ca). Seven of 16 individual differentiation batches showed a strong initial repolarization in the action potentials (AP) recorded from engineered heart tissue (EHT) followed by very early afterdepolarizations, sometimes even with consecutive oscillations. Iberiotoxin stopped oscillations and normalized AP shape, but had no effect in other EHTs without oscillations or in human left ventricular tissue (LV). Expression levels of the alpha-subunit (KCa1.1) of the BKCa correlated with the presence of oscillations in hiPSC-CMs and was not detectable in LV. Taken together, individual batches of hiPSC-CMs can express sarcolemmal ion channels that are otherwise not found in the human heart, resulting in oscillating afterdepolarizations in the AP. HiPSC-CMs should be screened for expression of non-cardiac ion channels before being applied to drug research.