Membrane remodelling triggers maturation of excitation-contraction coupling in 3D-shaped human-induced pluripotent stem cell-derived cardiomyocytes
The prospective use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for cardiac regenerative medicine strongly depends on the electro-mechanical properties of these cells, especially regarding the Ca2+-dependent excitation-contraction (EC) coupling mechanism. Currently, the...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 March 2023
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| In: |
Basic research in cardiology
Year: 2023, Volume: 118, Pages: 1-16 |
| ISSN: | 1435-1803 |
| DOI: | 10.1007/s00395-023-00984-5 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00395-023-00984-5 Verlag, kostenfrei, Volltext: https://link.springer.com/article/10.1007/s00395-023-00984-5 
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| Author Notes: | Fatemeh Kermani, Matias Mosqueira, Kyra Peters, Enrico D. Lemma, Kleopatra Rapti, Dirk Grimm, Martin Bastmeyer, Magdalena Laugsch, Markus Hecker, Nina D. Ullrich |
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| 245 | 1 | 0 | |a Membrane remodelling triggers maturation of excitation-contraction coupling in 3D-shaped human-induced pluripotent stem cell-derived cardiomyocytes |c Fatemeh Kermani, Matias Mosqueira, Kyra Peters, Enrico D. Lemma, Kleopatra Rapti, Dirk Grimm, Martin Bastmeyer, Magdalena Laugsch, Markus Hecker, Nina D. Ullrich |
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| 520 | |a The prospective use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for cardiac regenerative medicine strongly depends on the electro-mechanical properties of these cells, especially regarding the Ca2+-dependent excitation-contraction (EC) coupling mechanism. Currently, the immature structural and functional features of hiPSC-CM limit the progression towards clinical applications. Here, we show that a specific microarchitecture is essential for functional maturation of hiPSC-CM. Structural remodelling towards a cuboid cell shape and induction of BIN1, a facilitator of membrane invaginations, lead to transverse (t)-tubule-like structures. This transformation brings two Ca2+ channels critical for EC coupling in close proximity, the L-type Ca2+ channel at the sarcolemma and the ryanodine receptor at the sarcoplasmic reticulum. Consequently, the Ca2+-dependent functional interaction of these channels becomes more efficient, leading to improved spatio-temporal synchronisation of Ca2+ transients and higher EC coupling gain. Thus, functional maturation of hiPSC-cardiomyocytes by optimised cell microarchitecture needs to be considered for future cardiac regenerative approaches. | ||
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