ArticleCirculation research2012
Shortened Ca2+ signaling refractoriness underlies cellular arrhythmogenesis in a postinfarction model of sudden cardiac death.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 106 citations in OpenAlex.
- Restoration of mitochondrial CaJournal of molecular and cellular cardiology · 2026Article
- Ryanodine receptor 2 mutations in catecholaminergic polymorphic ventricular tachycardia: From molecular mechanisms to precision medicine.World journal of cardiology · 2026Review
- Novel Ca2+ wave mechanisms in cardiac myocytes revealed by multiscale Ca2+ release model.The Journal of general physiology · 2025Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- EuBiophysical journal · 2023Article
- Cardiomyocyte electrophysiology and its modulation: current views and future prospects.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Sexual dimorphism in bidirectional SR-mitochondria crosstalk in ventricular cardiomyocytes.Basic research in cardiology · 2023Article
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- CLIC4 localizes to mitochondrial-associated membranes and mediates cardioprotection.Science advances · 2022Article
- Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia.Circulation research · 2022Article
- ER stress and calcium-dependent arrhythmias.Frontiers in physiology · 2022Review
- Sodium-Glucose cotransporter 2 inhibitor empagliflozin decreases ventricular arrhythmia susceptibility by alleviating electrophysiological remodeling post-myocardial-infarction in mice.Frontiers in pharmacology · 2022Article
- Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control.American journal of physiology. Heart and circulatory physiology · 2022Article
- MCU overexpression evokes disparate dose-dependent effects on mito-ROS and spontaneous CaAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- Ventricular Arrhythmias in Ischemic Cardiomyopathy-New Avenues for Mechanism-Guided Treatment.Cells · 2021Review
- Determinants of Ca2+ release restitution: Insights from genetically altered animals and mathematical modeling.The Journal of general physiology · 2020Article
- Altered adrenergic response in myocytes bordering a chronic myocardial infarction underlies in vivo triggered activity and repolarization instability.The Journal of physiology · 2020Article
- Increased RyR2 activity is exacerbated by calcium leak-induced mitochondrial ROS.Basic research in cardiology · 2020Article
- Conditional Up-Regulation of SERCA2a Exacerbates RyR2-Dependent Ventricular and Atrial Arrhythmias.International journal of molecular sciences · 2020Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
rationaleDiastolic spontaneous Ca(2+) waves (DCWs) are recognized as important contributors to triggered arrhythmias. DCWs are thought to arise when [Ca(2+)] in sarcoplasmic reticulum ([Ca(2+)](SR)) reaches a certain threshold level, which might be reduced in cardiac disease as a consequence of sensitization of ryanodine receptors (RyR2s) to luminal Ca(2+).
objectiveWe investigated the mechanisms of DCW generation in myocytes from normal and diseased hearts, using a canine model of post-myocardial infarction ventricular fibrillation (VF). METHODS AND
resultsThe frequency of DCWs, recorded during periodic pacing in the presence of a β-adrenergic receptor agonist isoproterenol, was significantly higher in VF myocytes than in normal controls. Rather than occurring immediately on reaching a final [Ca(2+)](SR), DCWs arose with a distinct time delay after attaining steady [Ca(2+)](SR) in both experimental groups. Although the rate of [Ca(2+)](SR) recovery after the SR Ca(2+) release was similar between the groups, in VF myocytes the latency to DCWs was shorter, and the [Ca(2+)](SR) at DCW initiation was lower. The restitution of depolarization-induced Ca(2+) transients, assessed by a 2-pulse protocol, was significantly faster in VF myocytes than in controls. The VF-related alterations in myocyte Ca(2+) cycling were mimicked by the RyR2 agonist, caffeine. The reducing agent, mercaptopropionylglycine, or the CaMKII inhibitor, KN93, decreased DCW frequency and normalized restitution of Ca(2+) release in VF myocytes.
conclusionsThe attainment of a certain threshold [Ca(2+)](SR) is not sufficient for the generation of DCWs. Postrelease Ca(2+) signaling refractoriness critically influences the occurrence of DCWs. Shortened Ca(2+) signaling refractoriness due to RyR2 phosphorylation and oxidation is responsible for the increased rate of DCWs observed in VF myocytes and could provide a substrate for synchronization of arrhythmogenic events at the tissue level in hearts prone to VF.
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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.