Swynghedauw Bernard, Aubert Gaele
U572-INSERM Hôpital Lariboisière, Paris, France.
Exp Clin Cardiol. 2003 Fall;8(3):119-24.
This review analyzes recent data concerning the molecular determinants of repolarization time (RT) in normal and disease conditions. Considerations concerning the prognostic significance of RT were excluded. On a single normal cell, the duration of the action potential is the result of a balance between different ion currents. In vivo or on a multicellular preparation, the QT duration is modified by different transmural gradients, including the endo/epicardial gradient and the apex/base gradient. Spatial heterogeneity of the RT is not reflected by the range of the body surface QT dispersion. Inherited long QT syndrome is due to a gain or loss of function mutations located on the sodium current, the rapidly activating component of the delayed rectifier (I(Kr)) and the slowly activating component of the delayed rectifier. So far, no mutations have been detected on the transient outward K(+) current (I(tO)). Drug-induced long QT is caused by drugs that act as potassium blockers, which interact on specific domains of K(+) channel subunits, mainly on I(Kr). Several drugs may reveal 'forme frustes' of an inherited long QT. A prolonged RT is a well documented finding in cardiac hypertrophy and heart failure and is mostly caused by the noninduction and corresponding decreased density of the K(+) channel responsible for I(tO). Hypertrophy can even reverse the trans-mural gradient. In humans and rats, isolated pressure overload prolongs the QT interval. The reduction in I(tO) is likely to participate in the slowing of the cardiac cycle and reflects the re-expression of the fetal programme.
本综述分析了有关正常和疾病状态下复极时间（RT）分子决定因素的最新数据。排除了关于RT预后意义的考量。在单个正常细胞上，动作电位的持续时间是不同离子电流之间平衡的结果。在体内或多细胞制剂上，QT间期会因不同的跨壁梯度而改变，包括内膜/外膜梯度和心尖/心底梯度。体表QT离散度范围并未反映RT的空间异质性。遗传性长QT综合征是由于钠电流、延迟整流器的快速激活成分（I(Kr)）和延迟整流器的缓慢激活成分发生功能获得或丧失突变所致。到目前为止，尚未在瞬时外向K(+)电流（I(tO)）上检测到突变。药物诱导的长QT是由作为钾通道阻滞剂的药物引起的，这些药物作用于K(+)通道亚基的特定结构域，主要作用于I(Kr)。几种药物可能会揭示遗传性长QT的“顿挫型”。RT延长是心脏肥大和心力衰竭中一个有充分记录的发现，主要是由负责I(tO)的K(+)通道未诱导及相应密度降低所致。肥大甚至可以逆转跨壁梯度。在人类和大鼠中，孤立的压力超负荷会延长QT间期。I(tO)的降低可能参与了心动周期的减慢，并反映了胎儿程序的重新表达。
