title: Computational prediction of proarrhythmogenic effect of the V241F KCNQ1 mutation in human atrium.
abstract: Genetic factors play an important role in the pathogenesis of atrial flutter (AF). Although mutation in KCNQ1 has been widely correlated with AF, the mechanism by which mutation promotes AF remains poorly understood. The purpose of this study was to investigate the proarrhythmic effect of V241F KCNQ1 mutation in human atrium using the electrophysiological model of human atrium. Using 2D and 3D cardiac electrophysiological models that incorporate the Courtemanche human atrial model, we simulated electrical conduction through atrial tissue and compared spiral wave dynamics under the wild-type and V241F KCNQ1 conditions. In 2D and 3D simulation, V241F KCNQ1 showed a stable and persistent wave without spiral break-up, whereas the wild-type wave was less stable, resulting in early self-termination. According to the results, we concluded that compared to the wild type, the electrical activity of the V241F KCNQ1 mutation is more likely to sustain spiral wave.
authors.affiliation: Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Republic of Korea.
authors.forename: Riski
authors.initials: R
authors.lastname: Imaniastuti
authors.affiliation: Department of Mechanical & Biomedical Engineering, Kangwon National University, Republic of Korea.
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Inje University, Republic of Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Inje University, Republic of Korea.
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.affiliation: Department of Mechanical & Biomedical Engineering, Kangwon National University, Republic of Korea. Electronic address: ebshim@kangwon.ac.kr.
authors.forename: Eun Bo
authors.initials: EB
authors.lastname: Shim
authors.affiliation: Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Republic of Korea. Electronic address: kmlim@kumoh.ac.kr.
authors.forename: Ki Moo
authors.initials: KM
authors.lastname: Lim
mesh_terms: D001281:Atrial Fibrillation / Q000503:physiopathology*; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006325:Heart Atria / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008955:Models, Cardiovascular; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: Computational simulation; Spiral wave; V241F KCNQ mutation