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Open AccessArticle

Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes—An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca)

1
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
2
DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany
3
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, 6721 Szeged, Hungary
4
BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
5
Bioinformatics Core, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
6
Department of Cardiovascular Surgery, University Heart Center, 20246 Hamburg, Germany
7
Department of Cardiology-Electrophysiology, University Heart Center, 20246 Hamburg, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Current Address: Nanion Technologies GmbH, Ganghoferstraße 70a, 80339 München, Germany.
§
Current Address: Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cells 2020, 9(1), 253; https://doi.org/10.3390/cells9010253
Received: 28 October 2019 / Revised: 16 December 2019 / Accepted: 15 January 2020 / Published: 20 January 2020
(This article belongs to the Special Issue Stem Cell Research on Cardiology)
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. View Full-Text
Keywords: human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs); iPS cells; stem cells; big conductance calcium activated potassium channel (BK); Maxi-K; slo1; KCa1.1; iberiotoxin; long QT syndrome human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs); iPS cells; stem cells; big conductance calcium activated potassium channel (BK); Maxi-K; slo1; KCa1.1; iberiotoxin; long QT syndrome
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MDPI and ACS Style

Horváth, A.; Christ, T.; Koivumäki, J.T.; Prondzynski, M.; Zech, A.T.L.; Spohn, M.; Saleem, U.; Mannhardt, I.; Ulmer, B.; Girdauskas, E.; Meyer, C.; Hansen, A.; Eschenhagen, T.; Lemoine, M.D. Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes—An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca). Cells 2020, 9, 253. https://doi.org/10.3390/cells9010253

AMA Style

Horváth A, Christ T, Koivumäki JT, Prondzynski M, Zech ATL, Spohn M, Saleem U, Mannhardt I, Ulmer B, Girdauskas E, Meyer C, Hansen A, Eschenhagen T, Lemoine MD. Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes—An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca). Cells. 2020; 9(1):253. https://doi.org/10.3390/cells9010253

Chicago/Turabian Style

Horváth, András; Christ, Torsten; Koivumäki, Jussi T.; Prondzynski, Maksymilian; Zech, Antonia T.L.; Spohn, Michael; Saleem, Umber; Mannhardt, Ingra; Ulmer, Bärbel; Girdauskas, Evaldas; Meyer, Christian; Hansen, Arne; Eschenhagen, Thomas; Lemoine, Marc D. 2020. "Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes—An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca)" Cells 9, no. 1: 253. https://doi.org/10.3390/cells9010253

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