Link between SCN5A mutation and the brugada syndrome ECG phenotype - Simulation study
Link between SCN5A mutation and the brugada syndrome ECG phenotype - Simulation study
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DOI：
10.1253/circj.69.567
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Miyoshi, S;Mitamura, H;Ogawa, S
背景钠电流（I-Na）门控动力学的特定变化对其表型的影响仍有待阐明。在本研究中的门控动力学的变化INa对早期复极（ER）和启动2相折返（P2 R）的影响进行了评价，在一个理论的心外膜心室纤维model.Methods和结果Miyoshi-I-CaL被纳入修改后的Luo-Rudy动态（LRd）模型。在由具有间隙连接的连续排列的心外膜细胞组成的理论纤维内设置I-密度的分散。INa动力学发生了以下变化：（1）稳态失活的-10 mV偏移，（2）稳态激活曲线的+10 mV偏移，（3）小的失活时间常数（DEC）;观察到P2 R和ER。模拟了纤维内的传导干扰，只有当I-Na密度降低时，DEC才显示出引起ER和P2 R的可能性显着增加。结论在I-Na受体阻滞剂诱导ER的一维模型中，DEC-I-Na沉淀I-Na受体阻滞剂诱导ER。这表明，特征性ST段抬高的Brugada综合征与SCN 5A突变可以解释部分由DEC-I-Na。伴随的传导障碍可能需要在生理I-to密度下引起P2 R。
Background The specific changes in the gating kinetics of the sodium current (I-Na) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics Of INa on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model.Methods and Results Miyoshi-I-CaL was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at I-to-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in INa kinetics were made: (1) a -10 mV shift in steady-state inactivation, (2) a +10 mV shift in steady-state activation curve, (3) a small inactivation time constant (DEC); P2R and ER were observed. A conduction disturbance within the fiber was simulated and only when the I-Na-density was decreased did DEC, especially, show a marked increase in the likelihood of causing ER and P2R. Conduction disturbance significantly increased the likelihood causing ER or P2R.Conclusions In this one-dimension model with Ito-density dispersion, DEC-I-Na precipitates I-Na-blocker inducible ER. This suggests that the characteristic ST-segment elevation in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC-I-Na. Concomitant conduction disturbance may be required to cause P2R at physiological I-to density.