Investigating Arrhythmogenic Effects of the hERG Mutation N588K in Virtual Human Atria

机译：在虚拟人心房中研究hERG突变N588K的心律失常作用

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Atrial fibrillation (AF) is the most common cardiac arrhythmia in the western world. Genetic variants in the cardiac I_(kr) channel have been identified to influence ventricular repolarization. The aim of this work is to investigate the effect of the mutation N588K on atrial re-polarization and the predisposition to AF. Experimental data of N588K mutated hERG channel were incorporated in an atrial ionic model using parameter fitting. The effects of the mutation were analyzed in cell and tissue. N588K showed a gain of function effect, causing a rapid repolarization and a shortening of the action potential duration. Computer simulations of a schematic right atrial geometry were used to investigate the excitation conduction properties. The effective refractory period of mutant cells were reduced from 317 to 233 ms at 1 Hz. The conduction velocity is not significantly influenced by the mutation. Nevertheless, the wavelength of mutant cells is for all frequencies smaller, indicating that the mutation N588K predisposes the initiation and perpetuation of AF.

机译：心房颤动（AF）是西方世界最常见的心律不齐。心脏I_（kr）通道中的遗传变异已被发现会影响心室复极化。这项工作的目的是调查突变N588K对心房重新极化和房颤的易感性。使用参数拟合将N588K突变的hERG通道的实验数据纳入心房离子模型。在细胞和组织中分析了突变的影响。 N588K显示出功能效应的获得，引起快速的复极化和动作电位持续时间的缩短。右房几何图形的计算机模拟用于研究激发传导特性。突变细胞的有效不应期在1 Hz下从317毫秒减少到233毫秒。传导速度不受突变的影响很大。然而，突变细胞的波长对于所有频率而言都较小，这表明突变N588K倾向于AF的起始和持久。

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《Functional imaging and modeling of the heart》|2009年|144-153|共10页
会议地点 Nice(FR);Nice(FR)
作者
Gunnar Seemann; Paola Carillo; Daniel L. Weiss; Martin W. Krueger; Olaf Doessel; Eberhard P. Scholz;
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Institute of Biomedical Engineering, Universitaet Karlsruhe (TH), Kaiserstr. 12, 76131 Karlsruhe, Germany;

rnInstitute of Biomedical Engineering, Universitaet Karlsruhe (TH), Kaiserstr. 12, 76131 Karlsruhe, Germany;

rnInstitute of Biomedical Engineering, Universitaet Karlsruhe (TH), Kaiserstr. 12, 76131 Karlsruhe, Germany;

rnInstitute of Biomedical Engineering, Universitaet Karlsruhe (TH), Kaiserstr. 12, 76131 Karlsruhe, Germany;

rnInstitute of Biomedical Engineering, Universitaet Karlsruhe (TH), Kaiserstr. 12, 76131 Karlsruhe, Germany;

rnDept. of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany;

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正文语种 eng
中图分类心脏、血管（循环系）疾病;
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1. Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria [J] . Dominic G. Whittaker, Haibo Ni, Aziza El Harchi, PLoS Computational Biology . 2017,第6期

机译：短QT综合征中KCNJ2突变的心房脑肿瘤：虚拟人类阿里亚的见解
2. Quantitative prediction of the arrhythmogenic effects of de novo hERG mutations in computational models of human ventricular tissues [J] . Benson A.P., Al-Owais M., Holden A.V. European Biophysics Journal . 2011,第5期

机译：在人类心室组织计算模型中从头hERG突变的心律失常作用的定量预测
3. Quantitative prediction of the arrhythmogenic effects of de novo hERG mutations in computational models of human ventricular tissues [J] . Alan P. Benson, Moza Al-Owais, Arun V. Holden European Biophysics Journal . 2011,第5期

机译：在人心室组织计算模型中从头hERG突变的心律失常作用的定量预测
4. Investigating Arrhythmogenic Effects of the hERG Mutation N588K in Virtual Human Atria [C] . Gunnar Seemann, Paola Carillo, Daniel L. Weiss, International Conference on Functional Imaging and Modeling of the Heart . 2009

机译：研究HERG突变N588K在虚拟人体ATRIA中的心律源作用
5. Arrhythmogenic consequences of action potential duration gradients in the atria [D] . Ridler, Marc Etienne 2007

机译：心房中动作电位持续时间梯度的心律失常后果
6. Correction: Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria [O] . 2019

机译：校正：短QT综合征中KCNJ2突变的心律失常性：虚拟人心房的见解
7. Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome:Insights from virtual human atria [O] . Whittaker Dominic G, Ni Haibo, Harchi Aziza El, 2017

机译：短QT综合征中KCNJ2突变的心律失常性：来自虚拟人心房的见解

Investigating Arrhythmogenic Effects of the hERG Mutation N588K in Virtual Human Atria

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