ArticlePLoS computational biology2017
Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria.
Article in PLoS computational biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- A Novel KCNJ2 p.Glu299Ala Variant Associated with Short QT Phenotype and Persistent Atrial Fibrillation in a Child.Life (Basel, Switzerland) · 2026Article
- Biphasic effects on human atrial arrhythmogenicity of L-type calcium channel mutations associated with a Brugada/Short QT overlap syndrome - insights from a multiscale simulation study.PLoS computational biology · 2025Article
- Review
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of short QT syndrome type 3.Cardiovascular research · 2024Article
- Human atrial fibrillation and genetic defects in transient outward currents: mechanistic insights from multi-scale computational models.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Investigation of the Effects of the Short QT Syndrome D172N Kir2.1 Mutation on Ventricular Action Potential Profile Using Dynamic Clamp.Frontiers in pharmacology · 2021Article
- Calibration of ionic and cellular cardiac electrophysiology models.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Common Genetic Variants Modulate the Electrocardiographic Tpeak-to-Tend Interval.American journal of human genetics · 2020Article
- Computational Study to Identify the Effects of the KCNJ2 E299V Mutation in Cardiac Pumping Capacity.Computational and mathematical methods in medicine · 2020Article
- Investigation of the Role of Myocyte Orientations in Cardiac Arrhythmia Using Image-Based Models.Biophysical journal · 2019Article
- Understanding AF Mechanisms Through Computational Modelling and Simulations.Arrhythmia & electrophysiology review · 2019Review
- Correction: Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria.PLoS computational biology · 2019Article
- Proarrhythmia in the p.Met207Val PITX2c-Linked Familial Atrial Fibrillation-Insights From Modeling.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
- Differential Modulation ofFrontiers in physiology · 2019Article
- Genetics of atrial fibrillation: an update.Current opinion in cardiology · 2018Review
- Article
- Human Atrial Arrhythmogenesis and Sinus Bradycardia inFrontiers in physiology · 2018Article
- In silico investigation of a KCNQ1 mutation associated with short QT syndrome.Scientific reports · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2.1 mutations. Wild-type (WT) and mutant formulations were incorporated into multi-scale homogeneous and heterogeneous tissue models. Effects of mutations on AP duration (APD), conduction velocity (CV), effective refractory period (ERP), tissue excitation threshold and their rate-dependence, as well as the wavelength of re-entry (WL) were quantified. The D172N and E299V Kir2.1 mutations produced distinct effects on IK1 and APD shortening. Both mutations decreased WL for re-entry through a reduction in ERP and CV. Stability of re-entrant excitation waves in 2D and 3D tissue models was mediated by changes to tissue excitability and dispersion of APD in mutation conditions. Combined block of IK1 and IKr was effective in terminating re-entry associated with heterozygous D172N conditions, whereas IKr block alone may be a safer alternative for the E299V mutation. Combined inhibition of IKr and IKur produced a synergistic anti-arrhythmic effect in both forms of SQT3. In conclusion, this study provides mechanistic insights into atrial proarrhythmia with SQT3 Kir2.1 mutations and highlights possible pharmacological strategies for management of SQT3-linked AF.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.