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Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes

Van Meer, Berend J.; Krotenberg, Ana; Sala, Luca; Davis, Richard P; Eschenhagen, Thomas; Denning, Chris; Tertoolen, Leon G J; Mummery, Christine L; Mummery, Christine

Authors

Berend J. Van Meer

Ana Krotenberg

Luca Sala

Richard P Davis

Thomas Eschenhagen

Chris Denning

Leon G J Tertoolen

Christine L Mummery c.l.mummery@lumc.nl

Christine Mummery

Abstract

Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are increasingly recognized as valuable for determining the effects of drugs on ion channels but they do not always accurately predict contractile responses of the human heart. This is in part attributable to their immaturity but the sensitivity of measurement tools may also be limiting. Measuring action potential, calcium flux or contraction individually misses critical information that is captured when interrogating the complete excitation-contraction coupling cascade simultaneously. Here, we develop an hypothesis-based statistical algorithm that identifies mechanisms of action. We design and build a high-speed optical system to measure action potential, cytosolic calcium and contraction simultaneously using fluorescent sensors. These measurements are automatically processed, quantified and then assessed by the algorithm. Multiplexing these three critical physical features of hiPSC-CMs allows identification of all major drug classes affecting contractility with detection

Journal Article Type Article
Publication Date Sep 20, 2019
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 10
Article Number 4325
Institution Citation Van Meer, B. J., Krotenberg, A., Sala, L., Davis, R. P., Eschenhagen, T., Denning, C., …Mummery, C. (2019). Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes. Nature Communications, 10, https://doi.org/10.1038/s41467-019-12354-8
DOI https://doi.org/10.1038/s41467-019-12354-8
Publisher URL https://www.nature.com/articles/s41467-019-12354-8

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