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KMID : 0191120200350290238
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Journal of Korean Medical Science
2020 Volume.35 No. 29 p.238 ~ p.238
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Proarrhythmogenic Effect of the L532P and N588K KCNH2 Mutations in the Human Heart Using a 3D Electrophysiological Model
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Heikhmakhtiar Aulia Khamas
Abrha Abebe Tekle
Jeong Da-Un
Lim Ki-Moo
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Abstract
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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.
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KEYWORD
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KCNH2 Gene Mutation, L532P Mutation, N588K Mutation, Three-dimensional Heart Modeling
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