Journal
CELLS
Volume 9, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/cells9010253
Keywords
human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs); iPS cells; stem cells; big conductance calcium activated potassium channel (BK); Maxi-K; slo1; K-Ca1; 1; iberiotoxin; long QT syndrome
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Funding
- German Centre for Cardiovascular Research (DZHK)
- German Ministry of Research Education (BMBF)
- German Research Foundation (DFG) [3423/5-1]
- European Research Council [340248]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant (AFib-TrainNet) [675351]
- Research Promotion Fund of the Faculty of Medicine (Hamburg)
- Pirkanmaa Regional Fund of the Finnish Cultural Foundation
- Academy of Finland Centre of Excellence in Body-on-Chip Research
- European Research Council (ERC) [340248] Funding Source: European Research Council (ERC)
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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 (I-BK,I-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 (K(Ca)1.1) 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.
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