The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis.
The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis.
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DOI：
10.1111/j.1540-8167.2006.00388.x
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发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Belardinelli, Luiz
中科院分区：
文献类型：
--
作者：
Antzelevitch, Charles;Belardinelli, Luiz
大型哺乳动物的心室心肌由三种不同的细胞类型组成：心外膜细胞、M 细胞和心内膜细胞。心外膜和 M 细胞（而非心内膜细胞）的动作电位具有显着的 I(to) 介导的切迹。 M 细胞与其他细胞类型的区别在于它们显示较小的 I(Ks)，但显示较大的晚期 I(Na) 和 I(Na-Ca)。这些离子差异可能是 M 细胞更长的动作电位持续时间 (APD) 和更陡峭的 APD 速率关系的原因。第 1 相和第 3 相复极时程的差异分别有助于心电图 J 波和 T 波的记录。这些复极梯度由电紧张相互作用、[K(+)](o) 以及改变净复极电流的试剂或突变来调节。在各种病理生理状态下或对某些毒素作出反应时，晚期 I(Na) 增加会导致 M 细胞动作电位优先延长，从而延长 QT 间期并增加跨壁复极离散度 (TDR)，这是发生尖端扭转型室性心动过速 (TdP) 心律失常的基础。减少晚期 I(Na) 的药物可有效减少 TDR 和抑制 TdP。动作电位早期阶段峰值 I(Na) 的降低或净复极电流的增加可导致右心室心外膜动作电位优先缩短，从而导致大 TDR、2 相折返和与 Brugada 综合征相关的多形性室性心动过速。
Ventricular myocardium in larger mammals is composed of three distinct cell types: epicardial, M, and endocardial cells. Epicardial and M cell, but not endocardial cell, action potentials have a prominent I(to)-mediated notch. M cells are distinguished from the other cell types in that they display a smaller I(Ks), but a larger late I(Na) and I(Na-Ca). These ionic differences may account for the longer action potential duration (APD) and steeper APD-rate relationship of the M cell. The difference in the time course of repolarization of phase 1 and phase 3 contributes to the inscription of the electrocardiographic J wave and T wave, respectively. These repolarization gradients are modulated by electrotonic interactions, [K(+)](o), and agents or mutations that alter net repolarizing current. An increase in late I(Na), as occurring under a variety of pathophysiological states or in response to certain toxins, leads to a preferential prolongation of the M cell action potential, thus prolonging the QT interval and increasing transmural dispersion of repolarization (TDR), which underlies the development of torsade de pointes (TdP) arrhythmias. Agents that reduce late I(Na) are effective in reducing TDR and suppressing TdP. A reduction in peak I(Na) or an increase in net repolarizing current in the early phases of the action potential can lead to a preferential abbreviation of the action potential of epicardium in the right ventricle, and thus the development of a large TDR, phase 2 reentry, and polymorphic ventricular tachycardia associated with the Brugada syndrome.