Improving electrical properties of iPSC-cardiomyocytes by enhancing Cx43 expression

Journal of Molecular and Cellular Cardiology
Valentin SottasNina D Ullrich

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 (Nav1.5) 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 Nav1.5. Using transgenic approaches, Cx43 and Nav1.5 localization and cell coupling were studied by confocal imaging. Nav1.5 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 Nav1.5 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 pr...Continue Reading

Citations

Aug 23, 2020·International Journal of Molecular Sciences·Saltanat SmagulArman Saparov
Jan 5, 2021·Frontiers in Physiology·Caijuan DongTingzhong Wang
Dec 17, 2020·Journal of Cardiovascular Pharmacology·Michelangelo PaciJussi T Koivumäki

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