Role of HCN4 channel in preventing ventricular arrhythmia
Role of HCN4 channel in preventing ventricular arrhythmia
复制标题
DOI：
10.1038/jhg.2008.16
复制
发表时间：
2009-02
影响因子：
3.5
通讯作者：
K. Ueda;Y. Hirano;Y. Higashiuesato;Yoshiyasu Aizawa;Takeharu Hayashi;Natsuko F. Inagaki;T. Tana;Y. Ohya;S. Takishita;H. Muratani;M. Hiraoka;A. Kimura
中科院分区：
文献类型：
--
作者：
K. Ueda;Y. Hirano;Y. Higashiuesato;Yoshiyasu Aizawa;Takeharu Hayashi;Natsuko F. Inagaki;T. Tana;Y. Ohya;S. Takishita;H. Muratani;M. Hiraoka;A. Kimura
心动过缓是心律失常患者（包括 Brugada 综合征和长 QT 综合征）室性心律失常的触发因素。 HCN4 通道控制心率，其突变易导致遗传性病态窦房结综合征和与心动过缓相关的长 QT 综合征。我们在特发性室性心动过速患者的 HCN4 基因剪接供体位点发现了 4 个碱基插入，这应该会产生截短的通道。为了研究HCN4通道在室性心律失常中的作用，我们在计算机模拟模型中引入了HCN4产生的I f 通道的心室动作电位，发现I f 通道在心室动作电位的平台期产生泄漏向外电流。通过 If 通道的电流被认为有助于缩短动作电位持续时间并预防心动过缓的早期后除极。这些观察结果表明，HCN4 通道在触发心动过缓引起的室性心律失常方面发挥了预防作用。
Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the splice donor site of the HCN4 gene in a patient with idiopathic ventricular tachycardia, which was supposed to generate a truncated channel. To investigate the role of the HCN4 channel in ventricular arrhythmia, we introduced a ventricular action potential of I f channel produced by HCN4 in a computer simulation model and found that the I f channel generated a leaky outward current during the plateau phase of ventricular action potential. Currents through the I f channel were suggested to contribute to the shortening of the action potential duration and the prevention of early after-depolarization in bradycardia. These observations suggested that the HCN4 channel played a preventive role in triggering bradycardia-induced ventricular arrhythmias.