Proarrhythmogenic Effect of the L532P and N588K KCNH2 Mutations in the Human Heart Using a 3D Electrophysiological Model
10.3346/jkms.2020.35.e238
- Author:
Aulia Khamas HEIKHMAKHTIAR
1
;
Abebe Tekle ABRHA
;
Da Un JEONG
;
Ki Moo LIM
Author Information
1. School of Computing, Telkom University, Bandung, Jawa Barat, Indonesia
- Publication Type:Original Article
- From:Journal of Korean Medical Science
2020;35(29):e238-
- CountryRepublic of Korea
- Language:0
-
Abstract:
Background:Atrial arrhythmia is a cardiac disorder caused by abnormal electrical signaling and transmission, which can result in atrial fibrillation and eventual death. Genetic defects in ion channels can cause myocardial repolarization disorders. Arrhythmia-associated gene mutations, including KCNH2 gene mutations, which are one of the most common genetic disorders, have been reported. This mutation causes abnormal QT intervals by a gain of function in the rapid delayed rectifier potassium channel (IKr). In this study, we demonstrated that mutations in the KCNH2 gene cause atrial arrhythmia.
Methods:The N588K and L532P mutations were induced in the Courtemanche-Ramirez-Nattel (CRN) cell model, which was subjected to two-dimensional and three-dimensional simulations to compare the electrical conduction patterns of the wild-type and mutant-type genes.
Results:In contrast to the early self-termination of the wild-type conduction waveforms, the conduction waveform of the mutant-type retained the reentrant wave (N588K) and caused a spiral break-up, resulting in irregular wave generation (L532P).
Conclusion:The present study confirmed that the KCNH2 gene mutation increases the vulnerability of the atrial tissue for arrhythmia.
