ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Kcne3 deletion initiates extracardiac arrhythmogenesis in mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Clonal Hematopoiesis of Indeterminate Potential Proteomic Risk Score for Predicting Clinical Outcome in Patients With Heart Failure With Preserved Ejection Fraction.Circulation. Heart failure · 2026Article
- KCNE gene family: From basic functions to diseases.Genes & diseases · 2026Review
- Genetic Animal Models of Cardiovascular Pathologies.Biomedicines · 2025Review
- Identification of KCNE6, a new member of the KCNE family of potassium channel auxiliary subunits.Communications biology · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Kv Channel Ancillary Subunits: Where Do We Go from Here?Physiology (Bethesda, Md.) · 2022Review
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Fluorescence Fluctuation Spectroscopy enables quantification of potassium channel subunit dynamics and stoichiometry.Scientific reports · 2021Article
- The potassium channel Kcne3 is a VEGFA-inducible gene selectively expressed by vascular endothelial tip cells.Angiogenesis · 2020Article
- Deletion in mice of X-linked, Brugada syndrome- and atrial fibrillation-associated Kcne5 augments ventricular KFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Kcne4 deletion sex-specifically predisposes to cardiac arrhythmia via testosterone-dependent impairment of RISK/SAFE pathway induction in aged mice.Scientific reports · 2018Article
- Targeted deletion ofFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Article
- Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.Cardiovascular diabetology · 2017Article
- Regulation of human cardiac potassium channels by full-length KCNE3 and KCNE4.Scientific reports · 2016Article
- Novel exon 1 protein-coding regions N-terminally extend human KCNE3 and KCNE4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Kcne2 deletion attenuates acute post-ischaemia/reperfusion myocardial infarction.Cardiovascular research · 2016Article
- Review
- Kcne4 deletion sex- and age-specifically impairs cardiac repolarization in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Remote Liver Ischemic Preconditioning Protects against Sudden Cardiac Death via an ERK/GSK-3β-Dependent Mechanism.PloS one · 2016Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the human KCNE3 potassium channel ancillary subunit gene are associated with life-threatening ventricular arrhythmias. Most genes underlying inherited cardiac arrhythmias, including KCNE3, are not exclusively expressed in the heart, suggesting potentially complex disease etiologies. Here we investigated mechanisms of KCNE3-linked arrhythmogenesis in Kcne3(-/-) mice using real-time qPCR, echo- and electrocardiography, ventricular myocyte patch-clamp, coronary artery ligation/reperfusion, blood analysis, cardiac synaptosome exocytosis, microarray and pathway analysis, and multitissue histology. Kcne3 transcript was undetectable in adult mouse atria, ventricles, and adrenal glands, but Kcne3(-/-) mice exhibited 2.3-fold elevated serum aldosterone (P=0.003) and differentially expressed gene networks consistent with an adrenal-targeted autoimmune response. Furthermore, 8/8 Kcne3(-/-) mice vs. 0/8 Kcne3(+/+) mice exhibited an activated-lymphocyte adrenal infiltration (P=0.0002). Kcne3 deletion also caused aldosterone-dependent ventricular repolarization delay (19.6% mean QTc prolongation in females; P<0.05) and aldosterone-dependent predisposition to postischemia arrhythmogenesis. Thus, 5/11 Kcne3(-/-) mice vs. 0/10 Kcne3(+/+) mice exhibited sustained ventricular tachycardia during reperfusion (P<0.05). Kcne3 deletion is therefore arrhythmogenic by a novel mechanism in which secondary hyperaldosteronism, associated with an adrenal-specific lymphocyte infiltration, impairs ventricular repolarization. The findings highlight the importance of considering extracardiac pathogenesis when investigating arrhythmogenic mechanisms, even in inherited, monogenic channelopathies.
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