PDF(Pubmed)
Abstract：
In cardiac myocytes, the voltage-gated sodium channel NaV 1.5 opens in response to membrane depolarisation and initiates the action potential. The NaV 1.5 channel is typically associated with regulatory β-subunits that modify gating and trafficking behaviour. These β-subunits contain a single extracellular immunoglobulin (Ig) domain, a single transmembrane α-helix and an intracellular region. Here we focus on the role of the β1 and β3 subunits in regulating NaV 1.5. We catalogue β1 and β3 domain specific mutations that have been associated with inherited cardiac arrhythmia, including Brugada syndrome, long QT syndrome, atrial fibrillation and sudden death. We discuss how new structural insights into these proteins raises new questions about physiological function.
摘要：
在心肌细胞中，电压门控钠通道NaV1.5响应膜去极化而打开并启动动作电位。NaV1.5通道通常与调节门控和贩运行为的调节β亚基相关。这些β亚基包含单个细胞外免疫球蛋白（Ig）结构域，单个跨膜α-螺旋和细胞内区域。在这里，我们专注于β1和β3亚基在调节NaV1.5中的作用。我们对与遗传性心律失常相关的β1和β3结构域特异性突变进行分类，包括Brugada综合征,长QT综合征,心房颤动和猝死。我们讨论了对这些蛋白质的新结构见解如何引发有关生理功能的新问题。
