ArticleThe Journal of clinical investigation2016
Aberrant sodium influx causes cardiomyopathy and atrial fibrillation in mice.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
The trial behind it
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
52 citing papers in PubMed, 81 citations in OpenAlex.
- Three-dimensional visualization of arrhythmogenic substrate in mouse hearts using panoramic optical mapping and micro-computed tomography.Nature cardiovascular research · 2026Article
- Short SCN5A Transcript Yields a NaV1.5 Fragment Influencing Cardiac Metabolism.Circulation research · 2026Article
- Atrial fibrillation-induced neurocognitive and vascular dysfunction is averted by mitochondrial oxidative stress reduction.JCI insight · 2025Article
- Article
- Genetic Animal Models of Cardiovascular Pathologies.Biomedicines · 2025Review
- Automaticity of the Pulmonary Vein Myocardium and the Effect of Class I Antiarrhythmic Drugs.International journal of molecular sciences · 2024Review
- Quantitative 3D electron microscopy characterization of mitochondrial structure, mitophagy, and organelle interactions in murine atrial fibrillation.Journal of structural biology · 2024Article
- Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF.Cardiovascular research · 2024Article
- A membrane-associated phosphoswitch in Rad controls adrenergic regulation of cardiac calcium channels.The Journal of clinical investigation · 2024Article
- CaMKIIδ-dependent dysregulation of atrial NaFrontiers in pharmacology · 2024Article
- Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.Cardiovascular research · 2023Article
- Decreased FAM13B Expression Increases Atrial Fibrillation Susceptibility by Regulating Sodium Current and Calcium Handling.JACC. Basic to translational science · 2023Article
- Mouse models of spontaneous atrial fibrillation.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation.Molecular and cellular biochemistry · 2023Review
- Review
- Titin-truncating variants in hiPSC cardiomyocytes induce pathogenic proteinopathy and sarcomere defects with preserved core contractile machinery.Stem cell reports · 2023Article
- Rad regulation of CaNature cardiovascular research · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current.Nature cardiovascular research · 2022Article
- Adrenergic Regulation of Calcium Channels in the Heart.Annual review of physiology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Increased sodium influx via incomplete inactivation of the major cardiac sodium channel Na(V)1.5 is correlated with an increased incidence of atrial fibrillation (AF) in humans. Here, we sought to determine whether increased sodium entry is sufficient to cause the structural and electrophysiological perturbations that are required to initiate and sustain AF. We used mice expressing a human Na(V)1.5 variant with a mutation in the anesthetic-binding site (F1759A-Na(V)1.5) and demonstrated that incomplete Na+ channel inactivation is sufficient to drive structural alterations, including atrial and ventricular enlargement, myofibril disarray, fibrosis and mitochondrial injury, and electrophysiological dysfunctions that together lead to spontaneous and prolonged episodes of AF in these mice. Using this model, we determined that the increase in a persistent sodium current causes heterogeneously prolonged action potential duration and rotors, as well as wave and wavelets in the atria, and thereby mimics mechanistic theories that have been proposed for AF in humans. Acute inhibition of the sodium-calcium exchanger, which targets the downstream effects of enhanced sodium entry, markedly reduced the burden of AF and ventricular arrhythmias in this model, suggesting a potential therapeutic approach for AF. Together, our results indicate that these mice will be important for assessing the cellular mechanisms and potential effectiveness of antiarrhythmic therapies.
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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.