scholarly journals The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes inIn VitroCocultures

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Jan Trieschmann ◽  
Daniel Bettin ◽  
Moritz Haustein ◽  
Annette Köster ◽  
Marek Molcanyi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Action Potential ◽  
Embryonic Stem Cell ◽  
Interspike Interval ◽  
Cardiac Fibroblasts ◽  
Embryonic Stem ◽  
Therapeutic Approaches ◽  
Neonatal Cardiomyocytes ◽  
Repair Mechanisms ◽  
Upstroke Velocity

Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval:40.5±15.2% versus9.3±2.0%,p=0.008) and that action potential amplitude and maximal upstroke velocity (Vmax) were reduced (amplitude:52.3±1.7 mV versus65.1±1.5 mV,Vmax:7.0±1.0 V/s versus36.5±5.3 V/s), while action potential duration (APD) was prolonged (APD50:25.6±1.0 ms versus16.8±1.9 ms,p<0.001; APD90:52.2±1.5 ms versus43.3±3.3 ms,p<0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology.

scholarly journals Action Potential Modelling Predicts Electrophysiological and Pharmacological Features of Human Embryonic Stem Cell-derived Cardiomyocytes

2009 ◽  
Vol 96 (3) ◽  
pp. 664a
Author(s):  
Stefano Severi ◽  
Laura Sartiani ◽  
Marisa E. Jaconi ◽  
Alessandro Mugelli ◽  
Elisabetta Cerbai
Keyword(s):  
Stem Cell ◽  
Action Potential ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem

scholarly journals Functional Differences in Engineered Myocardium from Embryonic Stem Cell-Derived versus Neonatal Cardiomyocytes

2013 ◽  
Vol 1 (5) ◽  
pp. 387-396 ◽  
Author(s):  
Adam W. Feinberg ◽  
Crystal M. Ripplinger ◽  
Peter van der Meer ◽  
Sean P. Sheehy ◽  
Ibrahim Domian ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Neonatal Cardiomyocytes ◽  
Functional Differences

scholarly journals Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes

2012 ◽  
Vol 11 (1) ◽  
pp. 61 ◽  
Author(s):  
Michelangelo Paci ◽  
Laura Sartiani ◽  
Martina Del Lungo ◽  
Marisa Jaconi ◽  
Alessandro Mugelli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Action Potential ◽  
Mathematical Modelling ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem

scholarly journals Effect of Cardioactive Drugs on Action Potential Generation and Propagation in Embryonic Stem Cell-Derived Cardiomyocytes

2007 ◽  
Vol 19 (5-6) ◽  
pp. 213-224 ◽  
Author(s):  
Michael Reppel ◽  
Peter Igelmund ◽  
Ulrich Egert ◽  
Frieder Juchelka ◽  
Jürgen Hescheler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Action Potential ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Cardioactive Drugs

Action potential propagation failures in long-term recordings from embryonic stem cell-derived cardiomyocytes in tissue culture

1999 ◽  
Vol 437 (5) ◽  
pp. 669-679 ◽  
Author(s):  
Peter Igelmund ◽  
Bernd K. Fleischmann ◽  
Ivo R. Fischer ◽  
Julia Soest ◽  
Oleksii Gryshchenko ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Stem Cell ◽  
Action Potential ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Action Potential Propagation

scholarly journals TRPC7 regulates the electrophysiological functions of embryonic stem cell-derived cardiomyocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xianji Liu ◽  
Rui Zhao ◽  
Qianqian Ding ◽  
Xiaoqiang Yao ◽  
Suk Ying Tsang
Keyword(s):  
Stem Cell ◽  
Action Potential ◽  
Embryonic Stem Cell ◽  
Pluripotent Stem Cell ◽  
Transient Receptor Potential ◽  
Embryonic Stem ◽  
Receptor Potential ◽  
Dominant Negative ◽  
Sodium Calcium Exchanger ◽  
Action Potential Firing

Abstract Background Biological pacemakers consisting of pluripotent stem cell-derived cardiomyocytes are potentially useful for treating bradycardia. However, tachyarrhythmia caused by derived cardiomyocytes themselves is one of main barriers hampering their clinical translation. An in-depth understanding of the mechanisms underlying the spontaneous action potential (a.k.a. automaticity) might provide potential approaches to solve this problem. The aim of this project is to study the role of canonical transient receptor potential isoform 7 (TRPC7) channels in regulating the automaticity of embryonic stem cell-derived cardiomyocytes (ESC-CMs). Methods and results By Western blotting, the expression of TRPC7 was found to be increased during the differentiation of mouse ESC-CMs (mESC-CMs). Adenovirus-mediated TRPC7 knockdown decreased while overexpression increased the frequency of Ca2+ transients (CaTs), local Ca2+ releases (LCRs), and action potentials (APs) as detected by confocal microscopy and whole-cell patch-clamping. TRPC7 was found to be positively associated with the activity of ryanodine receptor 2 (RyR2), sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), and sodium-calcium exchanger (NCX) but not hyperpolarization-activated, cyclic nucleotide-gated channel (HCN), and inositol trisphosphate receptor (IP3R). Knockdown or overexpression of TRPC7 did not alter the expression of HCN4, Cav1.3, Cav3.1, Cav3.2, IP3R1, RyR2, and SERCA but positively regulated the phosphorylation of RyR2 at S2814 and phospholamban (PLN) at T17. Moreover, the positive regulation of APs by TRPC7 was Ca2+-dependent, as overexpression of N-terminus of TRPC7 (dominant negative of TRPC7) which diminished the Ca2+ permeability of TRPC7 decreased the AP frequency. Conclusions TRPC7 regulates the automaticity of mESC-CMs through two mechanisms. On the one hand, TRPC7 positively regulates the intracellular Ca2+ clock through the regulation of activities of both RyR2 and SERCA; on the other hand, TRPC7 also positively regulates the membrane clock via its influence on NCX activity. Altogether, our study reveals that TRPC7 is a potential drug target to manipulate the action potential firing rate of pluripotent stem cell-derived cardiomyocyte-based biological pacemakers to prevent tachyarrhythmia, a condition that might be encountered after transplantation.

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