Kcne3 deletion initiates extracardiac arrhythmogenesis in mice
| Autor: | Ritu Kant, Zhaoyang Hu, Shawn M. Crump, Geoffrey W. Abbott, Marie Anand, Roberto Levi |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Potassium Channels Microarray Long QT syndrome Biology Real-Time Polymerase Chain Reaction Biochemistry Research Communications Pathogenesis Electrocardiography Mice chemistry.chemical_compound Internal medicine Gene expression Genetics medicine Animals Aldosterone Molecular Biology medicine.diagnostic_test Arrhythmias Cardiac KCNE3 medicine.disease Mice Mutant Strains Potassium channel Endocrinology chemistry Potassium Channels Voltage-Gated cardiovascular system Female Biotechnology |
| Zdroj: | Hu, Z; Crump, SM; Anand, M; Kant, R; Levi, R; & Abbott, GW. (2014). Kcne3 deletion initiates extracardiac arrhythmogenesis in mice. FASEB Journal, 28(2), 935-945. doi: 10.1096/fj.13-241828. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/06f921zh |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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