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High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents
Open accessAbstract
Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes; however, the electrophysiological properties of hiPSC-derived cardiomyocytes have yet to be fully characterized. We performed detailed electrophysiological characterization of highly pure hiPSC-derived cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating cardiomyocytes using a perforated patch method and had atrial-, nodal-, and ventricular-like properties. Ventricular-like APs were more common and had maximum diastolic potentials close to those of human cardiac myocytes, AP durations were within the range of the normal human electrocardiographic QT interval, and APs showed expected sensitivity to multiple drugs (tetrodotoxin, nifedipine, and E4031). Early afterdepolarizations (EADs) were induced with E4031 and were bradycardia dependent, and EAD peak voltage varied inversely with the EAD take-off potential. Gating properties of seven ionic currents were studied including sodium ( I Na), L-type calcium ( I Ca), hyperpolarization-activated pacemaker ( I f), transient outward potassium ( I to), inward rectifier potassium ( I K1), and the rapidly and slowly activating components of delayed rectifier potassium ( I Kr and I Ks, respectively) current. The high purity and large cell numbers also enabled automated patch-clamp analysis. We conclude that these hiPSC-derived cardiomyocytes have ionic currents and channel gating properties underlying their APs and EADs that are quantitatively similar to those reported for human cardiac myocytes. These hiPSC-derived cardiomyocytes have the added advantage that they can be used in high-throughput assays, and they have the potential to impact multiple areas of cardiovascular research and therapeutic applications.
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Cites
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
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Self-citationHuman cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
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Patient-Specific Induced Pluripotent Stem-Cell Models for Long-QT Syndrome
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Karakikes, I., Ameen, M., Termglinchan, V., & Wu, J. C. (2015) · Circulation Research · doi:10.1161/circresaha.117.305365 · Cited by 478
Evolution of strategies to improve preclinical cardiac safety testing
Gintant, G., Sager, P. T., & Stockbridge, N. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.34 · Cited by 407
Human Engineered Heart Tissue: Analysis of Contractile Force
Mannhardt, I., Breckwoldt, K., Letuffe-Brenière, D., Schaaf, S., Schulz, H., Neuber, C., Benzin, A., Werner, T., Eder, A., Schulze, T., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.04.011 · Cited by 398
Metadata
- Authors
- Ma, J., Guo, L., Fiene, S. J., Anson, B. D., Thomson, J. A., Kamp, T. J., Kolaja, K. L., Swanson, B. J., & January, C. T.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2011-11
- Volume
- 301
- Issue
- 5
- Pages
- H2006-H2017
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2124929662
- Cited by
- 770
- References
- 7
- FWCI
- 25.02
- Type
- journal article
- Language
- en
- Open access
- green
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- Ma, J., Guo, L., Fiene, S. J., Anson, B. D., Thomson, J. A., Kamp, T. J., Kolaja, K. L., Swanson, B. J., & January, C. T. (2011). High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents. American Journal of Physiology-Heart and Circulatory Physiology. https://doi.org/10.1152/ajpheart.00694.2011
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