Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes

András Horváth, Marc D. Lemoine, Alexandra Löser, Ingra Mannhardt, Frederik Flenner, Ahmet Umur Uzun, Christiane Neuber, Kaja Breckwoldt, Arne Hansen, Evaldas Girdauskas, Hermann Reichenspurner, Stephan Willems, Norbert Jost, Erich Wettwer, Thomas Eschenhagen, Torsten Christ

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17 Citations (Scopus)

Abstract

Human induced pluripotent stem cell (hiPSC) cardiomyocytes (CMs) show less negative resting membrane potential (RMP), which is attributed to small inward rectifier currents (IK1). Here, IK1 was measured in hiPSC-CMs (proprietary and commercial cell line) cultured as monolayer (ML) or 3D engineered heart tissue (EHT) and, for direct comparison, in CMs from human right atrial (RA) and left ventricular (LV) tissue. RMP was measured in isolated cells and intact tissues. IK1 density in ML- and EHT-CMs from the proprietary line was similar to LV and RA, respectively. IK1 density in EHT-CMs from the commercial line was 2-fold smaller than in the proprietary line. RMP in EHT of both lines was similar to RA and LV. Repolarization fraction and IK,ACh response discriminated best between RA and LV and indicated predominantly ventricular phenotype in hiPSC-CMs/EHT. The data indicate that IK1 is not necessarily low in hiPSC-CMs, and technical issues may underlie low RMP in hiPSC-CMs. We show here that RMP is systematically underestimated in patch-clamped hiPSC-CMs and, in the 3D EHT format, reaches physiological values of human adult CMs when measured by sharp microelectrodes. This corresponds with IK1 currents as large as in human adult CMs. In human adult preparations, repolarization fraction was more useful than APD and RMP to classify action potentials as atrial or ventricular like.

Original languageEnglish
Pages (from-to)822-833
Number of pages12
JournalStem Cell Reports
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 13 2018

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Keywords

  • I
  • I
  • action potential duration
  • engineered heart tissue
  • human atrium
  • human induced pluripotent stem cell-derived cardiomyocytes
  • human ventricle
  • inward rectifier K current
  • repolarization fraction
  • resting membrane potential

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Horváth, A., Lemoine, M. D., Löser, A., Mannhardt, I., Flenner, F., Uzun, A. U., Neuber, C., Breckwoldt, K., Hansen, A., Girdauskas, E., Reichenspurner, H., Willems, S., Jost, N., Wettwer, E., Eschenhagen, T., & Christ, T. (2018). Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes. Stem Cell Reports, 10(3), 822-833. https://doi.org/10.1016/j.stemcr.2018.01.012