ArticlePflugers Archiv : European journal of physiology2014
A KCNQ1 mutation causes age-dependant bradycardia and persistent atrial fibrillation.
Article in Pflugers Archiv : European journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 38 citations in OpenAlex.
- Evaluation of the Potential Targets of Shenxian-Shengmai Oral Liquid in Treating Sick Sinus Syndrome Based on Network Pharmacology and Molecular Docking.Food science & nutrition · 2024Article
- Human Sinoatrial Node Pacemaker Activity: Role of the Slow Component of the Delayed Rectifier KInternational journal of molecular sciences · 2023Article
- Modulation of IJournal of cellular physiology · 2022Article
- Arrhythmogenic Effects of Genetic Mutations Affecting Potassium Channels in Human Atrial Fibrillation: A Simulation Study.Frontiers in physiology · 2021Article
- Prediction of Cardiac Mechanical Performance From Electrical Features During Ventricular Tachyarrhythmia Simulation Using Machine Learning Algorithms.Frontiers in physiology · 2020Article
- Computational Study to Identify the Effects of the KCNJ2 E299V Mutation in Cardiac Pumping Capacity.Computational and mathematical methods in medicine · 2020Article
- Characterization of a novel LQT3 variant with a selective efficacy of mexiletine treatment.Scientific reports · 2019Article
- Investigating the Complex Arrhythmic Phenotype Caused by the Gain-of-Function Mutation KCNQ1-G229D.Frontiers in physiology · 2019Article
- Understanding the Beat-to-Beat Variations of P-Waves Morphologies in AF Patients During Sinus Rhythm: A Scoping Review of the Atrial Simulation Studies.Frontiers in physiology · 2019Article
- Genetics of Atrial Fibrillation.Journal of the American Heart Association · 2018Review
- Effect of KCNQ1 G229D mutation on cardiac pumping efficacy and reentrant dynamics in ventricles: Computational study.International journal for numerical methods in biomedical engineering · 2018Article
- Computational analysis of the human sinus node action potential: model development and effects of mutations.The Journal of physiology · 2017Article
- Computational simulations of the effects of the G229D KCNQ1 mutation on human atrial fibrillation.The journal of physiological sciences : JPS · 2016Article
- Cardiac Delayed Rectifier Potassium Channels in Health and Disease.Cardiac electrophysiology clinics · 2016Review
- Genetics of atrial fibrillation: from families to genomes.Journal of human genetics · 2016Review
- Atrial fibrillation: mechanisms, therapeutics, and future directions.Comprehensive Physiology · 2015Review
- Your Father and Grandfather's Atrial Fibrillation: A Review of the Genetics of the Most Common Pathologic Cardiac Dysrhythmia.Current genomics · 2015Article
- Emerging directions in the genetics of atrial fibrillation.Circulation research · 2014Review
- Disease-linked supertrafficking of a potassium channel.The Journal of biological chemistryArticle
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atrial fibrillation (AF) is the most common arrhythmia. Gain-of-function mutations in KCNQ1, the pore-forming α-subunit of the slow delayed rectifier K current (IKs) channel, have been associated with AF. The purpose of this study was functional assessment of a mutation in KCNQ1 identified in a family with persistent AF and sinus bradycardia. We investigated whether this KCNQ1 missense mutation could form the genetic basis for AF and bradycardia simultaneously in this family. Sanger sequencing in a family with hereditary persistent AF identified a novel KCNQ1 variant (V241F) in a highly conserved region of S4 domain. The proband and her son developed bradycardia and persistent AF in an age-dependent fashion. The other son was a mutation carrier but he showed sinus bradycardia and not AF. Whole-cell patch clamp electrophysiology showed that V241F mutation in KCNQ1 shifted the activation curve to the left and dramatically slowed deactivation, leading to a constitutively open-like phenotype. Computer modeling showed that V241F would slow pacemaker activity. Also, simulations of atrial excitation predicted that V241F results in extreme shortening of action potential duration, possibly resulting in AF. Our study indicates that V241F might cause sinus bradycardia by increasing IKs. Additionally, V241F likely shortens atrial refractoriness to promote a substrate for reentry. KCNQ1 mutations have previously been described in AF, yet this is the first time a mutation in KCNQ1 is associated with age-dependent bradycardia and persistent AF. This finding further supports the hypothesis that sinus node dysfunction contributes to the development of AF.
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