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Journal of molecular and cellular cardiology v.120, 2018년, pp.31 - 41   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Improving electrical properties of iPSC-cardiomyocytes by enhancing Cx43 expression

Sottas, Valentin    (Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany   ); Wahl, Carl-Mattheis    (Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany   ); Trache, Mihnea C.    (Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany   ); Bartolf-Kopp, Michael    (Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany   ); Cambridge, Sidney    (Institute of Anatomy, Functional Neuroanatomy, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany   ); Hecker, Markus    (Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany   ); Ullrich, Nina D.    (Institute of Physiology and Pathophysiology, Division of Cardiovascular Physi  );
  • 초록  

    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 + channels (Na v 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 v 1.5. Using transgenic approaches, Cx43 and Na v 1.5 localization and cell coupling were studied by confocal imaging. Na v 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 v 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. Highlights Enhanced Cx43 expression leads to increased gap junction formation in iPSC-CMs. Spatio-temporal characteristics of signal propagation are significantly improved. Cx43 expression co-regulates Na v 1.5 ion channel function and myocyte excitability.


  • 주제어

    Pluripotent stem cell-derived cardiomyocytes .   Intercellular coupling .   Connexin-43 .   Nav1.   5 .   Excitability .   Action potential.  

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