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MODELING AND SIMULATION OF E1784K MUTATION AND SODIUM IONIC CHANNEL DISEASES

E1784K基因变异与钠离子通道病建模与仿真(英文)
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摘要 In the clinical reports, the E1784K mutation in SCN5A is recognized as a phenotypic overlap between the long QT syndrome (LQT3) and the Brugada syndrome (BrS) in the characteristics of electrocardiograms (ECGs) since the mutation can influence sodium channel functions. However it is still unclear if the E1784K mutation-induced sodium ionic channel alterations account for the overlap at tissue level. Thsu, a detailed computational model is developed to underpin the functional impacts of the E1784K mutation on the action potential (AP), the effective refractory period (ERP) and the abnormal ECG. Simulation results stlggest'that the E1784K mutation-induced sodium channel alterations are insufficient to produce the phenotypic overlap between LQT3 and BrS, and the overlap may arise from the complicated effects of the E1784K mutation-induced changes in sodium channel currents with an increase of the transient outward current ITo or a decrease of the L-type calcium current ICaL . 临床报道发现SCN5A上的一个位点突变E1784K基因变异会导致同时出现长QT间期III型综合征和Brugada综合征的特征。E1784K基因变异引起钠离子通道功能改变,但无法确定钠离子通道功能的改变是否能够解释LQT3和BrS交叠现象。为分析该问题,建立了详细的计算模型,从动作电位、有效不应期和伪心电图三方面进行仿真。仿真结果表明E1784K基因突变导致钠离子通道改变不能直接解释LQT3和BrS心电图特征交叠现象,而间接引起的ITo或者ICaL重构可以解释该现象。
出处 《Transactions of Nanjing University of Aeronautics and Astronautics》 EI 2011年第4期385-392,共8页 南京航空航天大学学报(英文版)
基金 Supported by the National Natural Science Foundation of China(61001167,61172149)~~
关键词 E1784K mutation sodium ionic channel long QT syndrome Brugada syndrome E1784K基因变异 钠离子通道 长QT间期Ⅲ型综合征 Brugada综合征
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参考文献12

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