title: Computational simulations of the effects of the G229D KCNQ1 mutation on human atrial fibrillation.
abstract: Atrial fibrillation (AF) is related to mutations at the genetic level. This includes mutations in genes that encode KCNQ1, a subunit of the I Ks channel. Here, we investigate the mechanism of gain-of-function in I Ks towards the occurrence of AF. We used the Courtemanche-Ramirez-Nattel (CRN) human atrial cell model (Am J Physiol Heart Circ Physiol 275:H301-H321, 1998) and applied the modification proposed by Hasegawa et al. (Heart Rhythm 11:67-75, 2014) to fit the behavior of I Ks due to the G229D mutation in KCNQ1 under a heterozygous mutant form. This was incorporated into two-(2D) and three-dimensional (3D) tissue models, where the mutation sustained a reentrant wave. However, under the wild-type condition, the reentrant wave terminated before the end of our simulations (in 2D, the spiral wave terminated before 10 s, while in 3D, the spiral wave terminated before 13 s). Sustained reentry under the mutation conditions also resulted in a spiral wave breakup in the 3D model, which was sustained until the end of the simulation (20 s), indicating AF.
authors.affiliation: Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Yangho-dong, Gumi, Gyeongbuk, 730-701, Republic of Korea.
authors.forename: Indana
authors.initials: I
authors.lastname: Zulfa
authors.affiliation: Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Eun Bo
authors.initials: EB
authors.lastname: Shim
authors.affiliation: Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Yangho-dong, Gumi, Gyeongbuk, 730-701, Republic of Korea.
authors.forename: Kwang-Soup
authors.initials: KS
authors.lastname: Song
authors.affiliation: Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Yangho-dong, Gumi, Gyeongbuk, 730-701, Republic of Korea. kmlim@kumoh.ac.kr.
authors.forename: Ki Moo
authors.initials: KM
authors.lastname: Lim
mesh_terms: D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology; D003198:Computer Simulation; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008955:Models, Cardiovascular; D009154:Mutation
chemical_list: D051657:KCNQ1 Potassium Channel
keywords: Arrhythmia; Atrial fibrillation; Gene mutation; KCNQ1