ArticleCirculation research2014
Optical mapping of sarcoplasmic reticulum Ca2+ in the intact heart: ryanodine receptor refractoriness during alternans and fibrillation.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.
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Who cites it
101 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation.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 · 2018Guideline
- Guideline
- Reduced Cx43 S-nitrosylation protects against cardiac stress-induced arrhythmias and myocardial injury in Duchenne muscular dystrophy.Cardiovascular research · 2026Article
- Presentation of preload and afterload to isolated heart preparations.The Journal of physiology · 2026Review
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- Spastin-mediated severing of glutamylated microtubules controls cardiomyocyte coupling.Nature cardiovascular research · 2026Article
- Magnetite Nanodiscs Activate Mechanotransductive Calcium Signaling in Diverse Cell Types.Journal of the American Chemical Society · 2025Article
- Dynamical instability is a major cause of cardiac action potential variability.Biophysical journal · 2025Article
- T-World: A highly general computational model of a human ventricular myocyte.bioRxiv : the preprint server for biology · 2025Article
- Pioglitazone Alleviates β1-adrenergic Receptor Antibody-induced Atrial Fibrillation SusceptivityCurrent medicinal chemistry · 2025Article
- Induction of cardiac alternans in human iPS-derived cardiomyocytes through β-adrenergic receptor stimulation.Physiological reports · 2024Article
- Hypertension-induced heart failure disrupts cardiac sympathetic innervation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Modeling sarcoplasmic reticulum CaBiophysics reports · 2024Article
- Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart.American journal of physiology. Heart and circulatory physiology · 2024Article
- Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.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 · 2024Review
- Brain-to-heart cholinergic synapse-calcium signaling mediates ischemic stroke-induced atrial fibrillation.Theranostics · 2024Article
- Native mechano-regulative matrix properties stabilize alternans dynamics and reduce spiral wave stabilization in cardiac tissue.Frontiers in network physiology · 2024Article
- Local Control Model of a Human Ventricular Myocyte: An Exploration of Frequency-Dependent Changes and Calcium Sparks.Biomolecules · 2023Article
- Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value.Nature communications · 2023Article
- Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
41 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
rationaleSarcoplasmic reticulum (SR) Ca(2+) cycling is key to normal excitation-contraction coupling but may also contribute to pathological cardiac alternans and arrhythmia.
objectiveTo measure intra-SR free [Ca(2+)] ([Ca(2+)]SR) changes in intact hearts during alternans and ventricular fibrillation (VF). METHODS AND
resultsSimultaneous optical mapping of Vm (with RH237) and [Ca(2+)]SR (with Fluo-5N AM) was performed in Langendorff-perfused rabbit hearts. Alternans and VF were induced by rapid pacing. SR Ca(2+) and action potential duration (APD) alternans occurred in-phase, but SR Ca(2+) alternans emerged first as cycle length was progressively reduced (217±10 versus 190±13 ms; P<0.05). Ryanodine receptor (RyR) refractoriness played a key role in the onset of SR Ca(2+) alternans, with SR Ca(2+) release alternans routinely occurring without changes in diastolic [Ca(2+)]SR. Sensitizing RyR with caffeine (200 μmol/L) significantly reduced the pacing threshold for both SR Ca(2+) and APD alternans (188±15 and 173±12 ms; P<0.05 versus baseline). Caffeine also reduced the magnitude of spatially discordant SR Ca(2+) alternans, but not APD alternans, the pacing threshold for discordance, or threshold for VF. During VF, [Ca(2+)]SR was high, but RyR remained nearly continuously refractory, resulting in minimal SR Ca(2+) release throughout VF.
conclusionsIn intact hearts, RyR refractoriness initiates SR Ca(2+) release alternans that can be amplified by diastolic [Ca(2+)]SR alternans and lead to APD alternans. Sensitizing RyR suppresses spatially concordant but not discordant SR Ca(2+) and APD alternans. Despite increased [Ca(2+)]SR during VF, SR Ca(2+) release was nearly continuously refractory. This novel method provides insight into SR Ca(2+) handling during cardiac alternans and arrhythmia.
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