ArticleBiophysical journal2011
Dynamics of calcium sparks and calcium leak in the heart.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 127 citations in OpenAlex.
- The RyR-like-FKBP12-PKA Complex Regulates Intracellular CaInternational journal of molecular sciences · 2026Article
- Adropin, S100A1, and SERCA2b Dysregulation in Coronary Artery Disease: Molecular and In Silico Insights into Calcium Signaling and Metabolic Dysfunction.Biomedicines · 2026Article
- Blink nadir measurements of sarcoplasmic reticulum are consistent with strong local CaBiophysical journal · 2025Article
- Gain-of-Function and Loss-of-Function Mutations in the RyR2-Expressing Gene Are Responsible for the CPVT1-Related Arrhythmogenic Activities in the Heart.Current issues in molecular biology · 2024Article
- Using a Failing Human Ventricular Cardiomyocyte Model to Re-Evaluate CaBiomolecules · 2024Article
- Structure, Function, and Regulation of the Junctophilin Family.Annual review of physiology · 2024Review
- Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.Journal of applied physics · 2023Article
- Local Control Model of a Human Ventricular Myocyte: An Exploration of Frequency-Dependent Changes and Calcium Sparks.Biomolecules · 2023Article
- S100 proteins in cardiovascular diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- ROCK (RhoA/Rho Kinase) Activation in Atrial Fibrillation: Molecular Pathways and Clinical Implications.Current cardiology reviews · 2023Article
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- SAR296968, a Novel Selective NaBiomedicines · 2022Article
- Critical Requirements for the Initiation of a Cardiac Arrhythmia in Rat Ventricle: How Many Myocytes?Cells · 2022Article
- Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.Frontiers in physiology · 2022Review
- ER stress and calcium-dependent arrhythmias.Frontiers in physiology · 2022Review
- Image-Driven Modeling of Nanoscopic Cardiac Function: Where Have We Come From, and Where Are We Going?Frontiers in physiology · 2022Review
- A Stochastic Spatiotemporal Model of Rat Ventricular Myocyte Calcium Dynamics Demonstrated Necessary Features for Calcium Wave Propagation.Membranes · 2021Article
- Cardiac Alternans Occurs through the Synergy of Voltage- and Calcium-Dependent Mechanisms.Membranes · 2021Article
- Phosphorylation of RyR2 Ser-2814 by CaMKII mediates β1-adrenergic stress induced CaFEBS open bio · 2021Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
We present what we believe to be a new mathematical model of Ca(2+) leak from the sarcoplasmic reticulum (SR) in the heart. To our knowledge, it is the first to incorporate a realistic number of Ca(2+)-release units, each containing a cluster of stochastically gating Ca(2+) channels (RyRs), whose biophysical properties (e.g., Ca(2+) sensitivity and allosteric interactions) are informed by the latest molecular investigations. This realistic model allows for the detailed characterization of RyR Ca(2+)-release properties, and shows how this balances reuptake by the SR Ca(2+) pump. Simulations reveal that SR Ca(2+) leak consists of brief but frequent single RyR openings (~3000 cell(-1) s(-1)) that are likely to be experimentally undetectable, and are, therefore, "invisible". We also observe that these single RyR openings can recruit additional RyRs to open, due to elevated local (Ca(2+)), and occasionally lead to the generation of Ca(2+) sparks (~130 cell(-1) s(-1)). Furthermore, this physiological formulation of "invisible" leak allows for the removal of the ad hoc, non-RyR mediated Ca(2+) leak terms present in prior models. Finally, our model shows how Ca(2+) sparks can be robustly triggered and terminated under both normal and pathological conditions. Together, these discoveries profoundly influence how we interpret and understand diverse experimental and clinical results from both normal and diseased hearts.
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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.