ArticleBiophysical journal2002
Termination of cardiac Ca(2+) sparks: an investigative mathematical model of calcium-induced calcium release.
Article in Biophysical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 181 papers.
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Who cites it
181 citing papers in PubMed, 293 citations in OpenAlex.
- Allosteric interactions between RyR channels justify intracellular Ca2+ release of skeletal muscle in quantitative detail.The Journal of general physiology · 2026Article
- Calmodulin controls spatial and temporal specificity of calcium-induced calcium release.PLoS computational biology · 2026Article
- Sequential Gating of Ryanodine Receptors Underlies the Development of Calcium Sparks in Frog Skeletal Muscle.Biomolecules · 2026Article
- Modeling the spatiotemporal properties of crosstalk between RyR-mediated and IPFrontiers in cell and developmental biology · 2026Article
- Calcium dynamics in small spaces: Lessons learned from modeling in dendritic spines.Biophysical journal · 2025Review
- Novel Ca2+ wave mechanisms in cardiac myocytes revealed by multiscale Ca2+ release model.The Journal of general physiology · 2025Article
- Blink nadir measurements of sarcoplasmic reticulum are consistent with strong local CaBiophysical journal · 2025Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- CaPhysiological reviews · 2024Review
- Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.Journal of applied physics · 2023Article
- EuBiophysical journal · 2023Article
- Local Control Model of a Human Ventricular Myocyte: An Exploration of Frequency-Dependent Changes and Calcium Sparks.Biomolecules · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Live-cell photo-activated localization microscopy correlates nanoscale ryanodine receptor configuration to calcium sparks in cardiomyocytes.Nature cardiovascular research · 2023Article
- The role of subunit cooperativity on ryanodine receptor 2 calcium signaling.Biophysical journal · 2023Article
- On the importance of ryanodine receptor subunit cooperativity in the heart.Biophysical journal · 2023Article
- Understanding Calmodulin Variants Affecting Calcium-Dependent Inactivation of L-Type Calcium Channels through Whole-Cell Simulation of the Cardiac Ventricular Myocyte.Biomolecules · 2022Article
- Avian cardiomyocyte architecture and what it reveals about the evolution of the vertebrate heart.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- The Role of CaBiomolecules · 2022Article
121 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A Ca(2+) spark arises when a cluster of sarcoplasmic reticulum (SR) channels (ryanodine receptors or RyRs) opens to release calcium in a locally regenerative manner. Normally triggered by Ca(2+) influx across the sarcolemmal or transverse tubule membrane neighboring the cluster, the Ca(2+) spark has been shown to be the elementary Ca(2+) signaling event of excitation-contraction coupling in heart muscle. However, the question of how the Ca(2+) spark terminates remains a central, unresolved issue. Here we present a new model, "sticky cluster," of SR Ca(2+) release that simulates Ca(2+) spark behavior and enables robust Ca(2+) spark termination. Two newly documented features of RyR behavior have been incorporated in this otherwise simple model: "coupled gating" and an opening rate that depends on SR lumenal [Ca(2+)]. Using a Monte Carlo method, local Ca(2+)-induced Ca(2+) release from clusters containing between 10 and 100 RyRs is modeled. After release is triggered, Ca(2+) flux from RyRs diffuses into the cytosol and binds to intracellular buffers and the fluorescent Ca(2+) indicator fluo-3 to produce the model Ca(2+) spark. Ca(2+) sparks generated by the sticky cluster model resemble those observed experimentally, and Ca(2+) spark duration and amplitude are largely insensitive to the number of RyRs in a cluster. As expected from heart cell investigation, the spontaneous Ca(2+) spark rate in the model increases with elevated cytosolic or SR lumenal [Ca(2+)]. Furthermore, reduction of RyR coupling leads to prolonged model Ca(2+) sparks just as treatment with FK506 lengthens Ca(2+) sparks in heart cells. This new model of Ca(2+) spark behavior provides a "proof of principle" test of a new hypothesis for Ca(2+) spark termination and reproduces critical features of Ca(2+) sparks observed experimentally.
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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.