Enhanced Na+ channel intermediate inactivation in Brugada syndrome
Enhanced Na+ channel intermediate inactivation in Brugada syndrome
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DOI：
10.1161/01.res.87.8.e37
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发表时间：
2000-10-13
影响因子：
20.1
通讯作者：
George, AL
中科院分区：
文献类型：
--
作者：
Wang, DW;Makita, N;George, AL
Brugada综合征是一种遗传性心脏病，在结构正常的心脏中引起与特发性室颤相关的猝死。该病的特征是右胸导联ST段抬高，常伴有明显的右冠状支传导阻滞。研究了与Brugada综合征相关的SCN 5A突变T1620 M的生物物理特性，以确定中间失活（I-M）缺陷，这是Na+通道中的门控过程，具有介于快速和缓慢失活之间的动力学特征。与野生型重组人心脏Na+通道（WT-hH 1）相比，在人β（1）亚基存在下表达T1620 M Na+通道的培养哺乳动物细胞在22 ℃和32 ℃下均表现出增强的中间失活。我们的研究结果支持了Brugada综合征的假设，部分原因是由于进入I-M状态的Na+通道比例增加而导致心肌中Na+电流功能降低。这种现象可能有助于显著的Brugada综合征患者的乳腺增生。这篇文章的全文可以在http://www.circresaha.org上找到。
Brugada syndrome is an inherited cardiac disease that causes sudden death related to idiopathic ventricular fibrillation in a structurally normal heart. The disease is characterized by ST-segment elevation in the right precordial ECG leads and is frequently accompanied by an apparent right bundle-branch block. The biophysical properties of the SCN5A mutation T1620M associated with Brugada syndrome were examined for defects in intermediate inactivation (I-M) a gating process in Na+ channels with kinetic features intermediate between fast and slow inactivation. Cultured mammalian cells expressing T1620M Na+ channels in the presence of the human beta (1) subunit exhibit enhanced intermediate inactivation at both 22 degreesC and 32 degreesC compared with wild-type recombinant human heart Na+ channels (WT-hH1). Our findings support the hypothesis that Brugada syndrome is caused, in part, by functionally reduced Na+ current in the myocardium due to an increased proportion of Na+ channels that enter the I-M state. This phenomenon may contribute significantly to arrhythmogenesis in patients with Brugada syndrome. The full text of this article is available at http://www.circresaha.org.