ArticleBiophysical journal2007
Enhanced ryanodine receptor-mediated calcium leak determines reduced sarcoplasmic reticulum calcium content in chronic canine heart failure.
Article in Biophysical journal, 2007. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 104 citations in OpenAlex.
- Restoration of mitochondrial CaJournal of molecular and cellular cardiology · 2026Article
- Catecholaminergic polymorphic ventricular tachycardia: A narrative review of recent advances in genetics, mechanisms, diagnosis, and treatment.Asian heart journal · 2025Review
- Improving effect of physical exercise on heart failure: Reducing oxidative stress-induced inflammation by restoring CaMolecular and cellular biochemistry · 2025Review
- Ion channel trafficking implications in heart failure.Frontiers in cardiovascular medicine · 2024Review
- EuBiophysical journal · 2023Article
- Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR).Nature communications · 2023Article
- Alterations of sarcoplasmic reticulum-mediated CaMolecular and cellular biochemistry · 2023Article
- Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury.International journal of molecular sciences · 2023Article
- CLIC4 localizes to mitochondrial-associated membranes and mediates cardioprotection.Science advances · 2022Article
- Interaction of background CaThe Journal of physiology · 2022Article
- Mitochondrial CaInternational journal of molecular sciences · 2022Review
- The function and regulation of calsequestrin-2: implications in calcium-mediated arrhythmias.Biophysical reviews · 2022Review
- Chai-Hu-San-Shen Capsule Ameliorates Ventricular Arrhythmia Through Inhibition of the CaMKII/FKBP12.6/RyR2/CaEvidence-based complementary and alternative medicine : eCAM · 2022Article
- MCU overexpression evokes disparate dose-dependent effects on mito-ROS and spontaneous CaAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- Stress-driven cardiac calcium mishandling via a kinase-to-kinase crosstalk.Pflugers Archiv : European journal of physiology · 2021Review
- Mitochondrial CaJournal of molecular and cellular cardiology · 2021Review
- Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target.Nature reviews. Cardiology · 2020Review
- Sarcoplasmic reticulum calcium mishandling: central tenet in heart failure?Biophysical reviews · 2020Review
- Increased RyR2 activity is exacerbated by calcium leak-induced mitochondrial ROS.Basic research in cardiology · 2020Article
- Nitric Oxide and Mechano-Electrical Transduction in Cardiomyocytes.Frontiers in physiology · 2020Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
In this study, we investigated the role of elevated sarcoplasmic reticulum (SR) Ca(2+) leak through ryanodine receptors (RyR2s) in heart failure (HF)-related abnormalities of intracellular Ca(2+) handling, using a canine model of chronic HF. The cytosolic Ca(2+) transients were reduced in amplitude and slowed in duration in HF myocytes compared with control, changes paralleled by a dramatic reduction in the total SR Ca(2+) content. Direct measurements of [Ca(2+)](SR) in both intact and permeabilized cardiac myocytes demonstrated that SR luminal [Ca(2+)] is markedly lowered in HF, suggesting that alterations in Ca(2+) transport rather than fractional SR volume reduction accounts for the diminished Ca(2+) release capacity of SR in HF. SR Ca(2+) ATPase (SERCA2)-mediated SR Ca(2+) uptake rate was not significantly altered, and Na(+)/Ca(2+) exchange activity was accelerated in HF myocytes. At the same time, SR Ca(2+) leak, measured directly as a loss of [Ca(2+)](SR) after inhibition of SERCA2 by thapsigargin, was markedly enhanced in HF myocytes. Moreover, the reduced [Ca(2+)](SR) in HF myocytes could be nearly completely restored by the RyR2 channel blocker ruthenium red. The effects of HF on cytosolic and SR luminal Ca(2+) signals could be reasonably well mimicked by the RyR2 channel agonist caffeine. Taken together, these results suggest that RyR2-mediated SR Ca(2+) leak is a major factor in the abnormal intracellular Ca(2+) handling that critically contributes to the reduced SR Ca(2+) content of failing cardiomyocytes.
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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.