ArticleCardiovascular research2015
Ryanodine receptor cluster fragmentation and redistribution in persistent atrial fibrillation enhance calcium release.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Modulated Calcium Homeostasis and Release Events Under Atrial Fibrillation and Its Risk Factors: A Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease.Acta physiologica (Oxford, England) · 2026Article
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026Review
- MINFLUX microscopy resolves subunits of the cardiac ryanodine receptor and its 3D orientation in cells.Nature communications · 2025Article
- Structural Integrity of RyR2 Clusters Controls Cardiac Calcium Leak.bioRxiv : the preprint server for biology · 2025Article
- Review
- The Multifaceted Role of Calcium Signaling in Regulated Necrosis.Biomolecules · 2025Review
- Sex Differences in Electrophysiology and Calcium Handling in Atrial Health and Fibrillation.Annual review of physiology · 2025Review
- Structural integrity of RyR2 clusters controls cardiac calcium leak.Frontiers in physiology · 2025Article
- Animal and cellular models of atrial fibrillation: a review.Frontiers in cardiovascular medicine · 2025Review
- Restoring Atrial T-Tubules Augments Systolic Ca Upon Recovery From Heart Failure.Circulation research · 2024Article
- Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation.Circulation · 2024Article
- BIN1 knockdown rescues systolic dysfunction in aging male mouse hearts.Nature communications · 2024Article
- Clustering properties of the cardiac ryanodine receptor in health and heart failure.Journal of molecular and cellular cardiology · 2023Review
- Cardiomyocyte ryanodine receptor clusters expand and coalesce after application of isoproterenol.The Journal of general physiology · 2023Article
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- Unveiling the intricacies of intracellular CaBiophysical journal · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
aimsIn atrial fibrillation (AF), abnormalities in Ca(2+) release contribute to arrhythmia generation and contractile dysfunction. We explore whether ryanodine receptor (RyR) cluster ultrastructure is altered and is associated with functional abnormalities in AF. METHODS AND
resultsUsing high-resolution confocal microscopy (STED), we examined RyR cluster morphology in fixed atrial myocytes from sheep with persistent AF (N = 6) and control (Ctrl; N = 6) animals. RyR clusters on average contained 15 contiguous RyRs; this did not differ between AF and Ctrl. However, the distance between clusters was significantly reduced in AF (288 ± 12 vs. 376 ± 17 nm). When RyR clusters were grouped into Ca(2+) release units (CRUs), i.e. clusters separated by <150 nm, CRUs in AF had more clusters (3.43 ± 0.10 vs. 2.95 ± 0.02 in Ctrl), which were more dispersed. Furthermore, in AF cells, more RyR clusters were found between Z lines. In parallel experiments, Ca(2+) sparks were monitored in live permeabilized myocytes. In AF, myocytes had >50% higher spark frequency with increased spark time to peak (TTP) and duration, and a higher incidence of macrosparks. A computational model of the CRU was used to simulate the morphological alterations observed in AF cells. Increasing cluster fragmentation to the level observed in AF cells caused the observed changes, i.e. higher spark frequency, increased TTP and duration; RyR clusters dispersed between Z-lines increased the occurrence of macrosparks.
conclusionIn persistent AF, ultrastructural reorganization of RyR clusters within CRUs is associated with overactive Ca(2+) release, increasing the likelihood of propagating Ca(2+) release.
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