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. 2019 Jun 25;9:9238. doi: 10.1038/s41598-019-45684-0

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Cell scale therapy modalities and resulting action potentials. (a) In cell delivery, remuscularized regions are represented as comprised of PSC-CMs only; shown are ionic currents of the PSC-CM membrane model. (b) Simulated PSC-CMs action potentials illustrate intrinsic automaticity arising from immaturity; a beat is generated every 1.6 s. (c) Induced cardiomyocytes (iCMs) arising from the transdifferentiation of fibroblasts electrically couple and exert an electrotonic effect on an adjacent, host ventricular CM; remuscularized regions are represented as comprised of a ventricular CM resistively coupled to multiple iCMs. The electrotonic effect of iCMs on a ventricular CM action potential is modulated by (d) the number of iCMs and (e) the junctional conductance. (d) Increasing the number of coupled iCMs from 0 to 8 results in prolongation of the ventricular CM action potential duration and increase in the phase I repolarization notch (inset); junctional conductance is 0.75 nS. (e) Spontaneous action potentials are observed in a ventricular CM coupled to 4 iCMs with junctional conductance of 1.25 nS. Transient subthreshold depolarizations occur at lower values of junctional conductance.