Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes
| Autor: | Luca Sala, Christine L. Mummery, Ana Krotenberg, Leon G.J. Tertoolen, Chris Denning, Berend J. van Meer, Richard P. Davis, Thomas Eschenhagen |
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| Přispěvatelé: | Applied Stem Cell Technologies, van Meer, B, Krotenberg, A, Sala, L, Davis, R, Eschenhagen, T, Denning, C, Tertoolen, L, Mummery, C |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Contraction (grammar) Science Induced Pluripotent Stem Cells Action Potentials General Physics and Astronomy Ion Channels Article Fluorescent dyes General Biochemistry Genetics and Molecular Biology Contractility cardiac arrhythmia 03 medical and health sciences 0302 clinical medicine Calcium flux Humans Computational models Myocyte pluripotent stem cell Myocytes Cardiac lcsh:Science Ion channel Calcium metabolism Multidisciplinary Chemistry Optical Imaging Excitation–contraction coupling Computational Biology Human heart General Chemistry Myocardial Contraction 3. Good health Electrophysiology 030104 developmental biology microscopy Biophysics lcsh:Q Calcium Algorithms 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019) Nature communications, 10(1):4325. Nature Publishing Group Nature Communications, 10 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-12354-8 |
| Popis: | 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 sensitivities higher than individual measurement of action potential, cytosolic calcium or contraction. Cardiomyocytes obtained from human induced pluripotent stem cells are increasingly used for drug testing, but they are not always predictive of the heart contractile responses. Here the authors develop a method to measure cytosolic calcium, action potentials and contraction simultaneously, to achieve higher sensitivity for drug screenings. |
| Databáze: | OpenAIRE |
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