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Verfasst von:Sottas, Valentin [VerfasserIn]   i
 Wahl, Carl-Mattheis [VerfasserIn]   i
 Trache, Cristian [VerfasserIn]   i
 Bartolf-Kopp, Michael [VerfasserIn]   i
 Cambridge, Sidney [VerfasserIn]   i
 Hecker, Markus [VerfasserIn]   i
 Ullrich, Nina D. [VerfasserIn]   i
Titel:Improving electrical properties of iPSC-cardiomyocytes by enhancing Cx43 expression
Verf.angabe:Valentin Sottas, Carl-Mattheis Wahl, Mihnea C. Trache, Michael Bartolf-Kopp, Sidney Cambridge, Markus Hecker, Nina D. Ullrich
E-Jahr:2018
Jahr:16 May 2018
Umfang:11 S.
Fussnoten:Gesehen am 30.03.2020
Titel Quelle:Enthalten in: Journal of molecular and cellular cardiology
Ort Quelle:New York, NY [u.a.] : Elsevier, 1970
Jahr Quelle:2018
Band/Heft Quelle:120(2018), Seite 31-41
ISSN Quelle:1095-8584
Abstract: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.
DOI:doi:10.1016/j.yjmcc.2018.05.010
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/j.yjmcc.2018.05.010
 Volltext: https://www.jmmc-online.com/article/S0022-2828(18)30171-8/abstract
 DOI: https://doi.org/10.1016/j.yjmcc.2018.05.010
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1693473941
Verknüpfungen:→ Zeitschrift

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