ArticleJournal of molecular and cellular cardiology2015
Mechanism of automaticity in cardiomyocytes derived from human induced pluripotent stem cells.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 111 citations in OpenAlex.
- In silico optimization of regenerative cell therapy in the infarcted human ventricles to mitigate arrhythmic burden.Stem cell reports · 2026Article
- Blebbistatin reduces calcium buffering in cardiomyocytes: Consequences for cellular electrophysiology.The Journal of physiology · 2026Article
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- Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC-cardiomyocytes vs. the adult human heart.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- A novel computational model of human iPSC-derived ventricular myocytes with improved L-type calcium current for application to Timothy syndrome.Scientific reports · 2026Article
- Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC-cardiomyocytes vs. the adult human heart.bioRxiv : the preprint server for biology · 2026Article
- Arrhythmogenic Risk in iPSC-Derived Cardiomyocytes: Current Limitations and Therapeutic Perspectives.Medicina (Kaunas, Lithuania) · 2025Review
- Optical mapping of the interface between iPSC-derived grafts and swine myocardium suggests potential arrhythmia mechanisms.NPJ Regenerative medicine · 2025Article
- Pluripotent stem cell-derived cardiomyocyte transplantation: marching from bench to bedside.Science China. Life sciences · 2025Review
- Article
- Maturation of human cardiac organoids enables complex disease modeling and drug discovery.Nature cardiovascular research · 2025Article
- Altered endoplasmic reticulum calcium loading in human PLN-R14del cardiomyopathy.Frontiers in cell and developmental biology · 2025Article
- Developing an approach for evaluating the cardiotoxic potential of botanicals.Frontiers in toxicology · 2025Review
- hiPSC-derived cardiac fibroblasts dynamically enhance the mechanical function of hiPSC-derived cardiomyocytes on an engineered substrate.Frontiers in bioengineering and biotechnology · 2025Article
- Connecting transcriptomics with computational modeling to reveal developmental adaptations in pediatric human atrial tissue.American journal of physiology. Heart and circulatory physiology · 2024Article
- Stem cell models of inherited arrhythmias.Nature cardiovascular research · 2024Review
- Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes.Biomolecules · 2024Article
- Nongenetic Optical Modulation of Pluripotent Stem Cells Derived Cardiomyocytes Function in the Red Spectral Range.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- CRISPRi gene modulation and all-optical electrophysiology in post-differentiated human iPSC-cardiomyocytes.Communications biology · 2023Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
objectivesThe creation of cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs) has spawned broad excitement borne out of the prospects to diagnose and treat cardiovascular diseases based on personalized medicine. A common feature of hiPS-CMs is their spontaneous contractions but the mechanism(s) remain uncertain.
methodsIntrinsic activity was investigated by the voltage-clamp technique, optical mapping of action potentials (APs) and intracellular Ca(2+) (Cai) transients (CaiT) at subcellular-resolution and pharmacological interventions.
resultsThe frequency of spontaneous CaiT (sCaiT) in monolayers of hiPS-CMs was not altered by ivabradine, an inhibitor of the pacemaker current, If despite high levels of HCN transcripts (1-4). HiPS-CMs had negligible If and IK1 (inwardly-rectifying K(+)-current) and a minimum diastolic potential of -59.1±3.3mV (n=18). APs upstrokes were preceded by a depolarizing-foot coincident with a rise of Cai. Subcellular Cai wavelets varied in amplitude, propagated and died-off; larger Cai-waves triggered cellular sCaTs and APs. SCaiTs increased in frequency with [Ca(2+)]out (0.05-to-1.8mM), isoproterenol (1μM) or caffeine (100μM) (n≥5, p<0.05). HiPS-CMs became quiescent with ryanodine receptor stabilizers (K201=2μM); tetracaine; Na-Ca exchange (NCX) inhibition (SEA0400=2μM); higher [K(+)]out (5→8mM), and thiol-reducing agents but could still be electrically stimulated to elicit CaiTs. Cell-cell coupling of hiPS-CM in monolayers was evident from connexin-43 expression and CaiT propagation. SCaiTs from an ensemble of dispersed hiPS-CMs were out-of-phase but became synchronous through the outgrowth of inter-connecting microtubules.
conclusionsAutomaticity in hiPS-CMs originates from a Ca(2+)-clock mechanism involving Ca(2+) cycling across the sarcoplasmic reticulum linked to NCX to trigger APs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.