ArticleCardiovascular research2014
Overexpression of KCNN3 results in sudden cardiac death.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
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- Transcriptomic Profiling of Human Myocardium at Sudden Death to Define Vulnerable Substrate for Lethal Arrhythmias.JACC. Clinical electrophysiology · 2025Article
- Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation.Nature communications · 2024Article
- Pathophysiology of Atrial Fibrillation and Approach to Therapy in Subjects Less than 60 Years Old.International journal of molecular sciences · 2024Review
- hiPSC-derived cardiomyocytes as a model to study the role of small-conductance CaFrontiers in cell and developmental biology · 2024Review
- Identification of immune-related genes for the diagnosis of ischemic heart failure based on bioinformatics.iScience · 2023Article
- Dual effects of the small-conductance CaAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Single-cell genomics improves the discovery of risk variants and genes of atrial fibrillation.Nature communications · 2023Article
- Loss of the Atrial Fibrillation-Related Gene,Circulation research · 2023Article
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- Overview of programmed electrical stimulation to assess atrial fibrillation susceptibility in mice.Frontiers in physiology · 2023Review
- Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation.JCI insight · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Cardiac small-conductance calcium-activated potassium channels in health and disease.Pflugers Archiv : European journal of physiology · 2021Review
- The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome.Pflugers Archiv : European journal of physiology · 2021Review
- Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase.Circulation · 2020Article
- Impact of IBiophysical journal · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundA recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias. METHODS AND
resultsWe characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T) mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3(T/T) mice have slower ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T) vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3(T/T) vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06).
conclusionOverexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction.
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