ArticleBasic research in cardiology2012
Proarrhythmia in a non-failing murine model of cardiac-specific Na+/Ca 2+ exchanger overexpression: whole heart and cellular mechanisms.
Article in Basic research in cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.Nature genetics · 2014Pooled it
- Annexin A4 Deficient Ventricular Myocytes Display Advanced Hypertrophy and Electrical Remodeling With Chronic β-Adrenoceptor Stimulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1.Nature communications · 2024Article
- Stress-Induced Proteasome Sub-Cellular Translocation in Cardiomyocytes Causes Altered Intracellular Calcium Handling and Arrhythmias.International journal of molecular sciences · 2024Article
- IncreasedInternational journal of cardiology. Heart & vasculature · 2023Article
- Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules · 2022Review
- Acute Genetic Ablation of Cardiac Sodium/Calcium Exchange in Adult Mice: Implications for Cardiomyocyte Calcium Regulation, Cardioprotection, and Arrhythmia.Journal of the American Heart Association · 2021Article
- Sarcoplasmic Reticulum Calcium Release Is Required for Arrhythmogenesis in the Mouse.Frontiers in physiology · 2021Article
- Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model:Frontiers in physiology · 2019Article
- Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity.Frontiers in physiology · 2018Review
- Distinct Occurrence of Proarrhythmic Afterdepolarizations in Atrial Versus Ventricular Cardiomyocytes: Implications for Translational Research on Atrial Arrhythmia.Frontiers in pharmacology · 2018Article
- The Effects of SEA0400 on CaFrontiers in pharmacology · 2017Article
- Arrhythmogenic effect of androgens on the rat heart.The journal of physiological sciences : JPS · 2017Article
- Electrophysiological alterations in a murine model of chronic coxsackievirus B3 myocarditis.PloS one · 2017Article
- Triggered activity in atrial myocytes is influenced by NaJournal of molecular and cellular cardiology · 2016Article
- Cardiac expression of the CREM repressor isoform CREM-IbΔC-X in mice leads to arrhythmogenic alterations in ventricular cardiomyocytes.Basic research in cardiology · 2016Article
- Nonequilibrium reactivation of Na+ current drives early afterdepolarizations in mouse ventricle.Circulation. Arrhythmia and electrophysiology · 2014Article
- Therapeutic safety of high myocardial expression levels of the molecular inotrope S100A1 in a preclinical heart failure model.Gene therapy · 2014Article
- Early afterdepolarizations in cardiac myocytes: beyond reduced repolarization reserve.Cardiovascular research · 2013Review
- Cardiac electrophysiology in mice: a matter of size.Frontiers in physiology · 2012Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The cardiac Na(+)/Ca(2+) exchanger (NCX) generates an inward electrical current during SR-Ca(2+) release, thus possibly promoting afterdepolarizations of the action potential (AP). We used transgenic mice 12.5 weeks or younger with cardiomyocyte-directed overexpression of NCX (NCX-Tg) to study the proarrhythmic potential and mechanisms of enhanced NCX activity. NCX-Tg exhibited normal echocardiographic left ventricular function and heart/body weight ratio, while the QT interval was prolonged in surface ECG recordings. Langendorff-perfused NCX-Tg, but not wild-type (WT) hearts, developed ventricular tachycardia. APs and ionic currents were measured in isolated cardiomyocytes. Cell capacitance was unaltered between groups. APs were prolonged in NCX-Tg versus WT myocytes along with voltage-activated K(+) currents (K(v)) not being reduced but even increased in amplitude. During abrupt changes in pacing cycle length, early afterdepolarizations (EADs) were frequently recorded in NCX-Tg but not in WT myocytes. Next to EADs, delayed afterdepolarizations (DAD) triggering spontaneous APs (sAPs) occurred in NCX-Tg but not in WT myocytes. To test whether sAPs were associated with spontaneous Ca(2+) release (sCR), Ca(2+) transients were recorded. Despite the absence of sAPs in WT, sCR was observed in myocytes of both genotypes suggesting a facilitated translation of sCR into DADs in NCX-Tg. Moreover, sCR was more frequent in NCX-Tg as compared to WT. Myocardial protein levels of Ca(2+)-handling proteins were not different between groups except the ryanodine receptor (RyR), which was increased in NCX-Tg versus WT. We conclude that NCX overexpression is proarrhythmic in a non-failing environment even in the absence of reduced K(V). The underlying mechanisms are: (1) occurrence of EADs due to delayed repolarization; (2) facilitated translation from sCR into DADs; (3) proneness to sCR possibly caused by altered Ca(2+) handling and/or increased RyR expression.
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