ArticleCirculation2014
Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation.
Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
257 citing papers in PubMed, 3 syntheses or guidelines pooled it, 448 citations in OpenAlex.
- Prevalence and risk factors for postoperative atrial fibrillation following pulmonary resection: a systematic review and meta-analysis.Journal of cardiothoracic surgery · 2026Pooled it
- Modulated Calcium Homeostasis and Release Events Under Atrial Fibrillation and Its Risk Factors: A Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation.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 · 2018Guideline
- A Mechanistic Clinical Trial Using (Circulation. Arrhythmia and electrophysiology · 2022Trial
- Rate control drugs differ in the prevention of progression of atrial fibrillation.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 · 2022Trial
- Arrhythmic events and genetic variants as drivers for Takotsubo Syndrome: a patient-specific atrial stem-cell model.Signal transduction and targeted therapy · 2026Article
- A modular method for high-throughput measurement of ion channel currents in cardiac myocytes.Nature protocols · 2026Review
- Flexoelectricity and ion transport synergy for high efficient energy conversion.Science advances · 2026Article
- Understanding the Diseased Atria.Physiology (Bethesda, Md.) · 2026Review
- Multiple 4q25 risk variants impair calcium homeostasis and compromise left atrial function.Cardiovascular research · 2026Article
- Blebbistatin reduces calcium buffering in cardiomyocytes: Consequences for cellular electrophysiology.The Journal of physiology · 2026Article
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease.Acta physiologica (Oxford, England) · 2026Article
- Use of soluble guanylyl cyclase stimulators in heart failure therapy-a mode of action perspective.ESC heart failure · 2026Review
- Review
- Cytosolic calcium handling signature: integration with clinical predictors enhances prediction of post-operative atrial fibrillation.European heart journal · 2026Article
- An epigenomic investigation of atrial fibrillation in a matched left and right atrial human cohort.Clinical epigenetics · 2026Article
- Modifiable Risk Factors in Atrial Fibrillation: Clinical Implications and Pathophysiological Insights.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2026Review
- Patient-reported effectiveness of strategies to convert paroxysmal atrial fibrillation to sinus rhythm in the home setting - a community-based participatory research approach.BMC cardiovascular disorders · 2026Article
- Spatially heterogeneous ionic remodelling promotes wavefront instability in simulated atrial tissue.Frontiers in network physiology · 2026Article
197 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundElectrical, structural, and Ca2+ -handling remodeling contribute to the perpetuation/progression of atrial fibrillation (AF). Recent evidence has suggested a role for spontaneous sarcoplasmic reticulum Ca2+ -release events in long-standing persistent AF, but the occurrence and mechanisms of sarcoplasmic reticulum Ca2+ -release events in paroxysmal AF (pAF) are unknown. METHOD AND
resultsRight-atrial appendages from control sinus rhythm patients or patients with pAF (last episode a median of 10-20 days preoperatively) were analyzed with simultaneous measurements of [Ca2+]i (fluo-3-acetoxymethyl ester) and membrane currents/action potentials (patch-clamp) in isolated atrial cardiomyocytes, and Western blot. Action potential duration, L-type Ca2+ current, and Na+ /Ca2+ -exchange current were unaltered in pAF, indicating the absence of AF-induced electrical remodeling. In contrast, there were increases in SR Ca2+ leak and incidence of delayed after-depolarizations in pAF. Ca2+ -transient amplitude and sarcoplasmic reticulum Ca2+ load (caffeine-induced Ca2+ -transient amplitude, integrated Na+/Ca2+ -exchange current) were larger in pAF. Ca2+ -transient decay was faster in pAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting increased SERCA2a function. In agreement, phosphorylation (inactivation) of the SERCA2a-inhibitor protein phospholamban was increased in pAF. Ryanodine receptor fractional phosphorylation was unaltered in pAF, whereas ryanodine receptor expression and single-channel open probability were increased. A novel computational model of the human atrial cardiomyocyte indicated that both ryanodine receptor dysregulation and enhanced SERCA2a activity promote increased sarcoplasmic reticulum Ca2+ leak and sarcoplasmic reticulum Ca2+ -release events, causing delayed after-depolarizations/triggered activity in pAF.
conclusionsIncreased diastolic sarcoplasmic reticulum Ca2+ leak and related delayed after-depolarizations/triggered activity promote cellular arrhythmogenesis in pAF patients. Biochemical, functional, and modeling studies point to a combination of increased sarcoplasmic reticulum Ca2+ load related to phospholamban hyperphosphorylation and ryanodine receptor dysregulation as underlying mechanisms.
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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.