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

Autor: Norbert Jost, Arne Hansen, K. Breckwoldt, Ingra Mannhardt, Hermann Reichenspurner, Christiane Neuber, Marc D Lemoine, Evaldas Girdauskas, Thomas Eschenhagen, Frederik Flenner, Alexandra Löser, Erich Wettwer, Torsten Christ, Stephan Willems, Ahmet Umur Uzun, András Horváth
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
inward rectifier K+ current
IK1
human atrium
resting membrane potential
Heart Ventricles
Potassium
Induced Pluripotent Stem Cells
Medizin
chemistry.chemical_element
030204 cardiovascular system & hematology
Biology
Biochemistry
Right atrial
Article
Membrane Potentials
action potential duration
03 medical and health sciences
0302 clinical medicine
health services administration
Genetics
Humans
Repolarization
Myocyte
Myocytes
Cardiac
human induced pluripotent stem cell-derived cardiomyocytes
Heart Atria
ddc:610
IK
ACh
Induced pluripotent stem cell
lcsh:QH301-705.5
health care economics and organizations
Membrane potential
lcsh:R5-920
human ventricle
Inward-rectifier potassium ion channel
Cell Biology
3. Good health
030104 developmental biology
chemistry
lcsh:Biology (General)
Cell culture
engineered heart tissue
Biophysics
lcsh:Medicine (General)
repolarization fraction
Developmental Biology
Zdroj: Stem Cell Reports, Vol 10, Iss 3, Pp 822-833 (2018)
Stem Cell Reports
ISSN: 2213-6711
Popis: Summary 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.
Highlights • Here, we report IK1 current density in hiPSC-CMs as high as in human adult CMs • Physiological RMP was found with sharp microelectrodes in engineered heart tissue • RMP measured by the patch-clamp technique in hiPSC-CMs may be underestimated • RMP and APD90 are not sufficient to categorize CMs as atrial or ventricular
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.
Databáze: OpenAIRE
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