Improving electrical properties of iPSC-cardiomyocytes by enhancing Cx43 expression
Abstract: The therapeutic potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is limited by immature functional features including low impulse propagation and reduced cell excitability. Key players regulating electrical activity are voltage-gated Na<sup>+</sup> c...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 May 2018
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| In: |
Journal of molecular and cellular cardiology
Year: 2018, Volume: 120, Pages: 31-41 |
| ISSN: | 1095-8584 |
| DOI: | 10.1016/j.yjmcc.2018.05.010 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.yjmcc.2018.05.010 Verlag, lizenzpflichtig, Volltext: https://www.jmmc-online.com/article/S0022-2828(18)30171-8/abstract 
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| Author Notes: | Valentin Sottas, Carl-Mattheis Wahl, Mihnea C. Trache, Michael Bartolf-Kopp, Sidney Cambridge, Markus Hecker, Nina D. Ullrich |
| Summary: | Abstract: The therapeutic potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is limited by immature functional features including low impulse propagation and reduced cell excitability. Key players regulating electrical activity are voltage-gated Na<sup>+</sup> channels (Na<sub>v</sub>1.5) and gap junctions built from connexin-43 (Cx43). Here we tested the hypothesis that enhanced Cx43 expression increases intercellular coupling and influences excitability by modulating Na<sub>v</sub>1.5. Using transgenic approaches, Cx43 and Na<sub>v</sub>1.5 localization and cell coupling were studied by confocal imaging. Na<sub>v</sub>1.5 currents and action potentials (APs) were measured using the patch-clamp technique. Enhanced sarcolemmal Cx43 expression significantly improved intercellular coupling and accelerated dye transfer kinetics. Furthermore, Cx43 modulated Na<sub>v</sub>1.5 function leading to significantly higher current and enhanced AP upstroke velocities, thereby improving electrical activity as measured by microelectrode arrays. These findings suggest a mechanistic link between cell coupling and excitability controlled by Cx43 expression in iPSC-CMs. Therefore, we propose Cx43 as novel molecular target for improving electrical properties of iPSC-CMs to match the functional properties of native myocytes. |
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| Item Description: | Gesehen am 30.03.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1095-8584 |
| DOI: | 10.1016/j.yjmcc.2018.05.010 |