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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: Kermani, Fatemeh (Author) , Mosqueira, Matias (Author) , Peters, Kyra (Author) , Lemma, Enrico D. (Author) , Rapti, Kleopatra (Author) , Grimm, Dirk (Author) , Bastmeyer, Martin (Author) , Laugsch, Magdalena (Author) , Hecker, Markus (Author) , Ullrich, Nina D. (Author)
Format: Article (Journal)
Language:English
Published: 29 March 2023
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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Summary: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.
Item Description:Gesehen am 12.06.2023
Physical Description:Online Resource
ISSN:1435-1803
DOI:10.1007/s00395-023-00984-5

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