ArticleProceedings of the National Academy of Sciences of the United States of America2007
Analysis of ryanodine receptor clusters in rat and human cardiac myocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 153 citations in OpenAlex.
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 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
- The emerging role of calsequestrin 2: from calcium sensor and modulator to arrhythmia driver.Journal of physiology and biochemistry · 2026Review
- Review
- Mechanism of Arrhythmogenesis Driven by Early After Depolarizations in Cardiac Tissue.PLoS computational biology · 2025Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- Clustering properties of the cardiac ryanodine receptor in health and heart failure.Journal of molecular and cellular cardiology · 2023Review
- CaJournal of molecular and cellular cardiology · 2023Article
- Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease.Open biology · 2023Article
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- Biological noise is a key determinant of the reproducibility and adaptability of cardiac pacemaking and EC coupling.The Journal of general physiology · 2022Review
- Mechanisms and physiological implications of cooperative gating of clustered ion channels.Physiological reviews · 2022Review
- CaCells · 2022Review
- The function and regulation of calsequestrin-2: implications in calcium-mediated arrhythmias.Biophysical reviews · 2022Review
- Image-Driven Modeling of Nanoscopic Cardiac Function: Where Have We Come From, and Where Are We Going?Frontiers in physiology · 2022Review
- In silico simulations reveal that RYR distribution affects the dynamics of calcium release in cardiac myocytes.The Journal of general physiology · 2021Article
- Nanoscale Organization, Regulation, and Dynamic Reorganization of Cardiac Calcium Channels.Frontiers in physiology · 2021Review
- Wenxin Keli for the Treatment of Arrhythmia-Systems Pharmacology andFrontiers in pharmacology · 2021Article
- Nanoscale Organisation of Ryanodine Receptors and Junctophilin-2 in the Failing Human Heart.Frontiers in physiology · 2021Article
- Human Atrial Fibrillation Is Not Associated With Remodeling of Ryanodine Receptor Clusters.Frontiers in cell and developmental biology · 2021Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Single rat ventricular myocytes and human ventricle tissue sections were labeled with antibodies against the ryanodine receptor (RyR) and alpha-actinin to examine the 3D distribution of RyRs with confocal microscopy. Image contrast was maximized by refractive index matching and deconvolution. The RyR label formed discrete puncta representing clusters of RyRs or "couplons" around the edges of the myofilaments with a nearest-neighbor spacing of 0.66 +/- 0.06 microm in rat and 0.78 +/- 0.07 microm in human. Each bundle of myofibrils was served by approximately six couplons, which supplied a cross-sectional area of approximately 0.6 microm(2) in rat and approximately 0.8 microm(2) in human. Although the couplons were in reasonable registration with z-lines, there were discontinuities in the longitudinal position of sarcomeres so that dislocations in the order of RyR clusters occurred. There was approximately 53% longitudinal registration of RyR clusters, suggesting a nonrandom placement of couplons around the sarcomere. These data can explain the spherical propagation of Ca(2+) waves and provide quantitative 3D data sets needed for accurate modeling of cardiac Ca(2+)-induced Ca(2+) release. By quantifying labeling intensity in rat ventricular myocytes, a lower limit of 78 RyRs per cluster (on average) was obtained. By modeling the couplon as a disk wrapping around a t-tubule and fitting cluster images, 95% of couplons contained between 120 and 260 RyRs (assuming that RyRs are tight packed with a spacing of 29 nm). Assuming similar labeling efficiency in human, from the fluorescence intensity alone we estimate that human ventricular myocytes contain approximately 30% fewer RyRs per couplon than rat.
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