ArticleHeart rhythm2008
Intracellular calcium leak due to FKBP12.6 deficiency in mice facilitates the inducibility of atrial fibrillation.
Article in Heart rhythm, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 128 citations in OpenAlex.
- A Mechanistic Clinical Trial Using (Circulation. Arrhythmia and electrophysiology · 2022Trial
- Destabilized calcium dynamics visualized using the genetically-coded probe GCaMPJ in intact hearts of Calstabin2-null mice.Frontiers in physiology · 2026Article
- Cryo-EM Brings the Mechanisms of Activation, Inactivation, and Inhibition of Ryanodine Receptors into Focus.Advances in experimental medicine and biology · 2026Review
- Cardiac FGF23 Increases Intracellular Calcium in Atrial Myocytes and the Susceptibility to Atrial Fibrillation Decreased in FGF23Journal of cellular and molecular medicine · 2025Article
- Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms.Aging cell · 2024Review
- SGLT2 inhibitors protect against diabetic cardiomyopathy and atrial fibrillation through a CaMKII independent mechanism.bioRxiv : the preprint server for biology · 2024Article
- Structural basis for ryanodine receptor type 2 leak in heart failure and arrhythmogenic disorders.Nature communications · 2024Article
- Catecholaminergic Polymorphic Ventricular Tachycardia: Multiple Clinical Presentations of a Genetically Determined Disease.Journal of clinical medicine · 2023Article
- NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- GBiomedicines · 2023Article
- Overview of programmed electrical stimulation to assess atrial fibrillation susceptibility in mice.Frontiers in physiology · 2023Review
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Preferential Expression of CaBiomolecules · 2022Article
- Homocysteine, Vitamins B6 and Folic Acid in Experimental Models of Myocardial Infarction and Heart Failure-How Strong Is That Link?Biomolecules · 2022Review
- Optimizing transesophageal atrial pacing in mice to detect atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2022Article
- Moving average and standard deviation thresholding (MAST): a novel algorithm for accurate R-wave detection in the murine electrocardiogram.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2021Article
- Attenuating persistent sodium current-induced atrial myopathy and fibrillation by preventing mitochondrial oxidative stress.JCI insight · 2021Article
- Inducibility, but not stability, of atrial fibrillation is increased by NOX2 overexpression in mice.Cardiovascular research · 2021Article
- The crosstalk between cardiomyocyte calcium and inflammasome signaling pathways in atrial fibrillation.Pflugers Archiv : European journal of physiology · 2021Review
- Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target.Nature reviews. Cardiology · 2020Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAlthough defective Ca(2+) homeostasis may contribute to arrhythmogenesis in atrial fibrillation (AF), the underlying molecular mechanisms remain poorly understood. Studies in patients with AF revealed that impaired diastolic closure of sarcoplasmic reticulum (SR) Ca(2+)-release channels (ryanodine receptors, RyR2) is associated with reduced levels of the RyR2-inhibitory subunit FKBP12.6.
objectiveThe objective of the present study was to test the hypothesis that Ca(2+) leak from the SR through RyR2 increases the propensity for AF in FKBP12.6-deficient (-/-) mice.
methodsSurface electrocardiogram and intracardiac electrograms were recorded simultaneously in FKBP12.6-/- mice and wild-type (WT) littermates. Right atrial programmed stimulation was performed before and after injection of RyR2 antagonist tetracaine (0.5 mg/kg). Intracellular Ca(2+) transients were recorded in atrial myocytes from FKBP12.6-/- and WT mice.
resultsFKBP12.6-/- mice had structurally normal atria and unaltered expression of key Ca(2+)-handling proteins. AF episodes were inducible in 81% of FKBP12.6-/-, but in only 7% of WT mice (P <.05), and were prevented by tetracaine in all FKBP12.6-/- mice. SR Ca(2+) leak in FKBP12.6-/- myocytes was 53% larger than in WT myocytes, and FKBP12.6-/- myocytes showed increased incidence of spontaneous SR Ca(2+) release events, which could be blocked by tetracaine.
conclusionThe increased vulnerability to AF in FKBP12.6-/- mice substantiates the notion that defective SR Ca(2+) release caused by abnormal RyR2 and FKBP12.6 interactions may contribute to the initiation or maintenance of atrial fibrillation.
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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.