ArticleThe Journal of clinical investigation2014
Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 5 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.
The trial behind it
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Who cites it
72 citing papers in PubMed, 5 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- The transcriptional landscape of atrial fibrillation: A systematic review and meta-analysis.PloS one · 2025Pooled 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
- Expert consensus document: Defining the major health modifiers causing atrial fibrillation: a roadmap to underpin personalized prevention and treatment.Nature reviews. Cardiology · 2016Guideline
- Guideline
- Sex differences in human atrial electrophysiology: the dark side of the moon? Will engineered heart tissue help to bring light into the darkness?Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Constitutive deletion of the obscurin-Ig58/59 domains induces atrial remodeling and Ca2+-based arrhythmogenesis.JCI insight · 2025Article
- Ryanodine receptor stabilization therapy suppresses CaJournal of molecular and cellular cardiology · 2024Article
- Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms.Aging cell · 2024Review
- Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation.Circulation · 2024Article
- Calcium-mediated DAD in membrane potentials and triggered activity in atrial myocytes of ETV1Journal of cellular and molecular medicine · 2024Article
- Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.Cardiovascular research · 2023Article
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.Biomolecules · 2023Review
- Review
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Enhanced CaCirculation research · 2023Article
- Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation.Journal of cardiovascular development and disease · 2023Article
- Increased β1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models.Clinical science (London, England : 1979) · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Atrial fibrillation (AF) is characterized by sustained high atrial activation rates and arrhythmogenic cellular Ca2+ signaling instability; however, it is not clear how a high atrial rate and Ca2+ instability may be related. Here, we characterized subcellular Ca2+ signaling after 5 days of high atrial rates in a rabbit model. While some changes were similar to those in persistent AF, we identified a distinct pattern of stabilized subcellular Ca2+ signaling. Ca2+ sparks, arrhythmogenic Ca2+ waves, sarcoplasmic reticulum (SR) Ca2+ leak, and SR Ca2+ content were largely unaltered. Based on computational analysis, these findings were consistent with a higher Ca2+ leak due to PKA-dependent phosphorylation of SR Ca2+ channels (RyR2s), fewer RyR2s, and smaller RyR2 clusters in the SR. We determined that less Ca2+ release per [Ca2+]i transient, increased Ca2+ buffering strength, shortened action potentials, and reduced L-type Ca2+ current contribute to a stunning reduction of intracellular Na+ concentration following rapid atrial pacing. In both patients with AF and in our rabbit model, this silencing led to failed propagation of the [Ca2+]i signal to the myocyte center. We conclude that sustained high atrial rates alone silence Ca2+ signaling and do not produce Ca2+ signaling instability, consistent with an adaptive molecular and cellular response to atrial tachycardia.
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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.