ArticleCardiovascular research2023
Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 34 citations in OpenAlex.
- A modular method for high-throughput measurement of ion channel currents in cardiac myocytes.Nature protocols · 2026Review
- Reconstructing AF-associated atrial fibrosis: Patient-specific iPSC models, fit-for-purpose atrial microphysiological systems, and nanomedicine.Materials today. Bio · 2026Review
- All-optical closed-loop control of human cardiomyocyte networks exploiting holographic optogenetics.Communications engineering · 2026Article
- Optogenetic tachypacing facilitates burst-induced arrhythmia in stem cell-derived human atrial engineered heart tissue.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Blebbistatin reduces calcium buffering in cardiomyocytes: Consequences for cellular electrophysiology.The Journal of physiology · 2026Article
- Divergent mitochondrial and fibrotic signatures in atrial fibrillation: insights from organoids and GEO data.Cardiovascular diabetology · 2026Article
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- Arrhythmia-induced cardiomyopathy: focus on atrial fibrillation.Nature reviews. Cardiology · 2026Review
- Human iPSCs: atrial versus ventricular cardiomyocytes and their functional and pharmacological differences.Biochemical Society transactions · 2026Review
- Chamber-specific chromatin architecture guides functional interpretation of disease-associated Cis-regulatory elements in human cardiomyocytes.Nature communications · 2026Article
- Targeted nanodelivery strategies for atrial fibrillation: concomitant targeting of fibrosis suppression and electrical conduction restoration through advanced nanobiotechnology.Journal of nanobiotechnology · 2025Review
- Article
- Mitochondria-Targeted Antioxidants Prevent Tachypacing-Induced Contractile Dysfunction in In Vitro Cardiomyocyte and In VivoAntioxidants (Basel, Switzerland) · 2025Article
- Arrhythmogenic Risk in iPSC-Derived Cardiomyocytes: Current Limitations and Therapeutic Perspectives.Medicina (Kaunas, Lithuania) · 2025Review
- Apremilast improves cardiomyocyte cohesion and arrhythmia in different models for arrhythmogenic cardiomyopathy.Stem cell research & therapy · 2025Article
- Stem cell-derived heterocellular atrial engineered cardiac tissue with comparisons to native human atrial myocardium.American journal of physiology. Heart and circulatory physiology · 2025Article
- High Rate Triggers Increased Atrial Release of BMP10, A Biomarker for Atrial Fibrillation and Stroke, and BMP10 Affects Ventricular Cardiomyocytes.Circulation. Arrhythmia and electrophysiology · 2025Article
- The role of iPSC research for insight into inherited arrhythmia conditions.Heart rhythm · 2025Review
- Arrhythmia-Induced Cardiomyopathy in Atrial Fibrillation: Pathogenesis, Diagnosis, and Treatment.Life (Basel, Switzerland) · 2025Review
- PFKM-Driven Lactate Overproduction Promotes Atrial Fibrillation via Triggering Cardiac Fibroblasts Histone Lactylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 1 country.
Funding
Abstract
aimsAtrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies is hampered by the absence of scalable experimental human models that reflect AF-associated electrical remodelling. Therefore, we aimed to assess if AF-associated remodelling of cellular electrophysiology can be simulated in human atrial-like cardiomyocytes derived from induced pluripotent stem cells in the presence of retinoic acid (iPSC-aCM), and atrial-engineered human myocardium (aEHM) under short term (24 h) and chronic (7 days) tachypacing (TP). METHODS AND
resultsFirst, 24-h electrical pacing at 3 Hz was used to investigate whether AF-associated remodelling in iPSC-aCM and aEHM would ensue. Compared to controls (24 h, 1 Hz pacing) TP-stimulated iPSC-aCM presented classical hallmarks of AF-associated remodelling: (i) decreased L-type Ca2+ current (ICa,L) and (ii) impaired activation of acetylcholine-activated inward-rectifier K+ current (IK,ACh). This resulted in action potential shortening and an absent response to the M-receptor agonist carbachol in both iPSC-aCM and aEHM subjected to TP. Accordingly, mRNA expression of the channel-subunit Kir3.4 was reduced. Selective IK,ACh blockade with tertiapin reduced basal inward-rectifier K+ current only in iPSC-aCM subjected to TP, thereby unmasking an agonist-independent constitutively active IK,ACh. To allow for long-term TP, we developed iPSC-aCM and aEHM expressing the light-gated ion-channel f-Chrimson. The same hallmarks of AF-associated remodelling were observed after optical-TP. In addition, continuous TP (7 days) led to (i) increased amplitude of inward-rectifier K+ current (IK1), (ii) hyperpolarization of the resting membrane potential, (iii) increased action potential-amplitude and upstroke velocity as well as (iv) reversibly impaired contractile function in aEHM.
conclusionsClassical hallmarks of AF-associated remodelling were mimicked through TP of iPSC-aCM and aEHM. The use of the ultrafast f-Chrimson depolarizing ion channel allowed us to model the time-dependence of AF-associated remodelling in vitro for the first time. The observation of electrical remodelling with associated reversible contractile dysfunction offers a novel platform for human-centric discovery of antiarrhythmic therapies.
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Registered trials
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.