ArticleCirculation research2012
Ryanodine receptor current amplitude controls Ca2+ sparks in cardiac muscle.
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 47 papers.
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Who cites it
47 citing papers in PubMed.
- Destabilized calcium dynamics visualized using the genetically-coded probe GCaMPJ in intact hearts of Calstabin2-null mice.Frontiers in physiology · 2026Article
- Modeling the spatiotemporal properties of crosstalk between RyR-mediated and IPFrontiers in cell and developmental biology · 2026Article
- Novel Ca2+ wave mechanisms in cardiac myocytes revealed by multiscale Ca2+ release model.The Journal of general physiology · 2025Article
- Electrophysical cardiac remodeling at the molecular level: Insights into ryanodine receptor activation and calcium-induced calcium release from a stochastic explicit-particle model.Biophysical journal · 2024Article
- Isolated Cardiac Ryanodine Receptor Function Varies Between Mammals.The Journal of membrane biology · 2024Article
- The Structural-Functional Crosstalk of the Calsequestrin System: Insights and Pathological Implications.Biomolecules · 2023Review
- EuBiophysical journal · 2023Article
- Local Control Model of a Human Ventricular Myocyte: An Exploration of Frequency-Dependent Changes and Calcium Sparks.Biomolecules · 2023Article
- High-resolution analysis of the cytosolic CaAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Article
- Age-related Loss of miR-124 Causes Cognitive DeficitsAging and disease · 2022Article
- Cytosolic Ca2+-dependent Ca2+ release activity primarily determines the ER Ca2+ level in cells expressing the CPVT-linked mutant RYR2.The Journal of general physiology · 2022Article
- Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels.Frontiers in endocrinology · 2022Article
- Three-Dimensional Model of Sub-Plasmalemmal CaFrontiers in molecular biosciences · 2022Article
- Image-Driven Modeling of Nanoscopic Cardiac Function: Where Have We Come From, and Where Are We Going?Frontiers in physiology · 2022Review
- The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes.Pflugers Archiv : European journal of physiology · 2021Review
- A high throughput machine-learning driven analysis of CaCell calcium · 2020Article
- Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats.Cell calcium · 2020Article
- Regulation of the RyR channel gating by CaBiophysical reviews · 2018Review
- Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis.Circulation research · 2018Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
rationaleIn cardiac muscle, Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) is mediated by ryanodine receptor (RyR) Ca(2+) release channels. The inherent positive feedback of CICR is normally well-controlled. Understanding this control mechanism is a priority because its malfunction has life-threatening consequences.
objectiveWe show that CICR local control is governed by SR Ca(2+) load, largely because load determines the single RyR current amplitude that drives inter-RyR CICR. METHODS AND
resultsWe differentially manipulated single RyR Ca(2+) flux amplitude and SR Ca(2+) load in permeabilized ventricular myocytes as an endogenous cell biology model of the heart. Large RyR-permeable organic cations were used to interfere with Ca(2+) conductance through the open RyR pore. Single-channel studies show this attenuates current amplitude without altering other aspects of RyR function. In cells, the same experimental maneuver increased resting SR Ca(2+) load. Despite the increased load, Ca(2+) spark (inter-RyR CICR events) frequency decreased and sparks terminated earlier.
conclusionsSpark local control follows single RyR current amplitude, not simply SR Ca(2+) load. Spark frequency increases with load because spontaneous RyR openings at high loads produce larger currents (ie, a larger CICR trigger signal). Sparks terminate when load falls to the point at which single RyR current amplitude is no longer sufficient to sustain inter-RyR CICR. Thus, RyRs that spontaneously close no longer reopen and local Ca(2+) release ends.
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