Abstract：
Nav1.5 is the main voltage-gated sodium channel found in cardiac muscle, where it facilitates the fast influx of Na+ ions across the cell membrane, resulting in the fast depolarization phase-phase 0 of the cardiac action potential. As a result, it plays a major role in determining the amplitude and the upstroke velocity of the cardiac impulse. Quantitively, cardiac sodium channel activates in less than a millisecond to trigger the cardiac action potential and inactivates within 2-3 ms to facilitate repolarization and return to the resting state in preparation for firing the next action potential. Missense mutations in the gene that encodes Nav1.5 (SCN5A), change these time constants which leads to a wide spectrum of cardiac diseases ranging from long QT syndrome type 3 (LQT3) to sudden cardiac death. In this mini-review I will focus on the missense mutations in the inactivation gate of Nav1.5 that results in arrhythmia, attempting to correlate the location of the missense mutation to their specific phenotype.
摘要：
Nav1.5是心肌中发现的主要电压门控钠通道，它促进Na+离子快速流入细胞膜，导致心脏动作电位的快速去极化阶段0。因此,它在确定心脏冲动的幅度和上冲程速度中起着重要作用。定量地,心脏钠通道在不到一毫秒的时间内激活以触发心脏动作电位，并在2-3ms内失活以促进复极化并返回静息状态，为激发下一个动作电位做准备。编码Nav1.5（SCN5A）的基因中的错义突变，改变这些时间常数，导致广泛的心脏疾病，从长QT综合征3型（LQT3）到心脏猝死。在这篇小型评论中，我将重点关注Nav1.5失活门中导致心律失常的错义突变，试图将错义突变的位置与其特定表型相关联。
