ArticleCirculation. Arrhythmia and electrophysiology2012
Size and ionic currents of unexcitable cells coupled to cardiomyocytes distinctly modulate cardiac action potential shape and pacemaking activity in micropatterned cell pairs.
Article in Circulation. Arrhythmia and electrophysiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Connexin 43-Enriched Vesicles Improve Synchronization in hiPSC-Derived Cardiomyocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Heterogeneity of ventricular action potentials in neonatal rat cardiomyocytes and methodological aspects of patch clamp measurements.Frontiers in physiology · 2025Article
- Computational design of custom therapeutic cells to correct failing human cardiomyocytes.Frontiers in systems biology · 2023Article
- Microfluidics-Based Single-Cell Research for Intercellular Interaction.Frontiers in cell and developmental biology · 2021Review
- Quantifying the effects of engineered nanomaterials on endothelial cell architecture and vascular barrier integrity using a cell pair model.Nanoscale · 2019Article
- Altering integrin engagement regulates membrane localization of KJournal of cell science · 2019Article
- Article
- GAmerican journal of physiology. Heart and circulatory physiology · 2017Article
- In vitro models of the cardiac microenvironment to study myocyte and non-myocyte crosstalk: bioinspired approaches beyond the polystyrene dish.The Journal of physiology · 2017Review
- Age-dependent functional crosstalk between cardiac fibroblasts and cardiomyocytes in a 3D engineered cardiac tissue.Acta biomaterialia · 2017Article
- Differential Mechanisms of Myocardial Conduction Slowing by Adipose Tissue-Derived Stromal Cells Derived from Different Species.Stem cells translational medicine · 2017Article
- Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing.Frontiers in physiology · 2017Review
- A Systemized Approach to Investigate Ca(2+) Synchronization in Clusters of Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes.Frontiers in cell and developmental biology · 2015Article
- Review
- Quantifying electrical interactions between cardiomyocytes and other cells in micropatterned cell pairs.Methods in molecular biology (Clifton, N.J.) · 2014Article
- Design and formulation of functional pluripotent stem cell-derived cardiac microtissues.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Spatial profiles of electrical mismatch determine vulnerability to conduction failure across a host-donor cell interface.Circulation. Arrhythmia and electrophysiology · 2013Article
- Article
- The origin and arrhythmogenic potential of fibroblasts in cardiac disease.Journal of cardiovascular translational research · 2012Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCardiac cell therapies can yield electric coupling of unexcitable donor cells to host cardiomyocytes with functional consequences that remain unexplored. METHODS AND
resultsWe micropatterned cell pairs consisting of a neonatal rat ventricular myocyte (NRVM) coupled to an engineered human embryonic kidney 293 (HEK293) cell expressing either connexin-43 (Cx43 HEK) or inward rectifier potassium channel 2.1 (Kir2.1) and Cx43 (Kir2.1+Cx43 HEK). The NRVM-HEK contact length was fixed yielding a coupling strength of 68.9±9.7 nS, whereas HEK size was systematically varied. With increase in Cx43 HEK size, NRVM maximal diastolic potential was reduced from -71.7±0.6 mV in single NRVMs to -35.1±1.3 mV in pairs with an HEK:NRVM cell surface area ratio of 1.7±0.1, whereas the action potential upstroke ([dV(m)/dt](max)) and duration decreased to 1.6±0.7% and increased to 177±32% in single NRVM values, respectively (n=21 cell pairs). Pacemaking occurred in all NRVM-Cx43 HEK pairs with cell surface area ratios of 1.1 to 1.9. In contrast, NRVMs, coupled with Kir2.1+Cx43 HEKs of increasing size, had similar maximal diastolic potentials, exhibited no spontaneous activity, and showed a gradual decrease in action potential duration (n=23). Furthermore, coupling single NRVMs to a dynamic clamp model of HEK cell ionic current reproduced the cardiac maximal diastolic potentials and pacemaking rates recorded in cell pairs, whereas reproducing changes in (dV(m)/dt)(max) and action potential duration required coupling to an HEK model that also included cell membrane capacitance.
conclusionsSize and ionic currents of unexcitable cells electrically coupled to cardiomyocytes distinctly affect cardiac action potential shape and initiation with important implications for the safety of cardiac cell and gene therapies.
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