ArticleCardiovascular research2011
Recovery of cardiac calcium release is controlled by sarcoplasmic reticulum refilling and ryanodine receptor sensitivity.
Article in Cardiovascular research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 90 citations in OpenAlex.
- Ca2+ signalling in cardiac muscle: the importance of balances.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 · 2026Review
- Modeling the spatiotemporal properties of crosstalk between RyR-mediated and IPFrontiers in cell and developmental biology · 2026Article
- Compromised repolarization reserve in a murine model of catecholaminergic polymorphic ventricular tachycardia caused by RyR2-R420Q mutation.Journal of molecular and cellular cardiology · 2025Article
- EuBiophysical journal · 2023Article
- Local Control Model of a Human Ventricular Myocyte: An Exploration of Frequency-Dependent Changes and Calcium Sparks.Biomolecules · 2023Article
- Live-cell photo-activated localization microscopy correlates nanoscale ryanodine receptor configuration to calcium sparks in cardiomyocytes.Nature cardiovascular research · 2023Article
- Cardiac Alternans: From Bedside to Bench and Back.Circulation research · 2023Review
- Synchronization of spatially discordant voltage and calcium alternans in cardiac tissue.Physical review. E · 2022Article
- SPEG: a key regulator of cardiac calcium homeostasis.Cardiovascular research · 2021Review
- Local recovery of cardiac calcium-induced calcium release interrogated by ultra-effective, two-photon uncaging of calcium.The Journal of physiology · 2021Article
- Blockade of sodium‑calcium exchanger via ORM-10962 attenuates cardiac alternans.Journal of molecular and cellular cardiology · 2021Article
- Determinants of Ca2+ release restitution: Insights from genetically altered animals and mathematical modeling.The Journal of general physiology · 2020Article
- Loss of SPEG Inhibitory Phosphorylation of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation.Circulation · 2020Article
- Quantitative tests reveal that microtubules tune the healthy heart but underlie arrhythmias in pathology.The Journal of physiology · 2020Article
- Recruiting RyRs to Open in a CaBiophysical journal · 2020Article
- Phosphorylation of the ryanodine receptor 2 at serine 2030 is required for a complete β-adrenergic response.The Journal of general physiology · 2019Article
- IOCBIO Sparks detection and analysis software.PeerJ · 2019Article
- NCX-Mediated Subcellular CaBiophysical journal · 2018Article
- Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin-Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia.Journal of the American Heart Association · 2018Article
- Modulation of Cardiac Alternans by Altered Sarcoplasmic Reticulum Calcium Release: A Simulation Study.Frontiers in physiology · 2018Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsIn heart cells, the mechanisms underlying refractoriness of the elementary units of sarcoplasmic reticulum (SR) Ca(2+) release, Ca(2+) sparks, remain unclear. We investigated local recovery of SR Ca(2+) release using experimental measurements and mathematical modelling. METHODS AND
resultsRepeated Ca(2+) sparks were induced from individual clusters of ryanodine receptors (RyRs) in quiescent rat ventricular myocytes, and we examined how changes in RyR gating influenced the time-dependent recovery of Ca(2+) spark amplitude and triggering probability. Repeated Ca(2+) sparks from individual sites were analysed in the presence of 50 nM ryanodine with: (i) no additional agents (control); (ii) 50 µM caffeine to sensitize RyRs; (iii) 50 µM tetracaine to inhibit RyRs; or (iv) 100 nM isoproterenol to activate β-adrenergic receptors. Sensitization and inhibition of RyR clusters shortened and lengthened, respectively, the median interval between consecutive Ca(2+) sparks (caffeine 239 ms; control 280 ms; tetracaine 453 ms). Recovery of Ca(2+) spark amplitude, however, was exponential with a time constant of ∼100 ms in all cases. Isoproterenol both accelerated the recovery of Ca(2+) spark amplitude (τ = 58 ms) and shortened the median interval between Ca(2+) sparks (192 ms). The results were recapitulated by a mathematical model in which SR [Ca(2+)] depletion terminates Ca(2+) sparks, but not by an alternative model based on limited depletion and Ca(2+)-dependent inactivation of RyRs.
conclusionTogether, the results strongly suggest that: (i) local SR refilling controls Ca(2+) spark amplitude recovery; (ii) Ca(2+) spark triggering depends on both refilling and RyR sensitivity; and (iii) β-adrenergic stimulation influences both processes.
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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.