Role of IKur in controlling action potential shape and contractility in the human atrium -: Influence of chronic atrial fibrillation
Role of IKur in controlling action potential shape and contractility in the human atrium -: Influence of chronic atrial fibrillation
复制标题
DOI：
10.1161/01.cir.0000145155.60288.71
复制
发表时间：
2004-10-19
期刊：
影响因子：
37.8
通讯作者：
Ravens, U
中科院分区：
文献类型：
--
作者：
Wettwer, E;Hála, O;Ravens, U
背景-超快向外电流I-Kur是人类心房的主要复极电流，是治疗心房心律失常的潜在靶点。研究了低浓度4-氨基吡啶或联苯衍生物av0118选择性阻断I-Kur对窦性心律（SR）或慢性心房颤动（AF）患者小梁右房动作电位（APs）的影响。方法与结果- AF组在90%复极时的AP持续时间（APD(90)）短于SR组（300 +/- 16 ms, n = 6, 414 +/- 10 ms, n = 15），而APD（20）长（AF组35 +/- 9 ms， SR组5 +/- 2 ms， P < 0.05）。4-氨基吡啶（5 μmol/L）使高原电位从SR的- 21 +/- 3提高到- 6 +/- 3 mV，使AF的0 +/- 3提高到+ 12 +/- 3 mV，使APD从SR的414 +/- 10 ms可逆缩短到350 +/- 10 ms，使AF的APD从300 +/- 16 ms可逆延长到320 +/- 13 ms， AVE 0118 （6 μmol/L）的结果与之相似。人类心房ap中I-Kur阻滞的计算机模拟预测了I-Ca、I-L以及向外变流器I-Kr和I-Ks的继发性增加，AF的变化小于sr。4-氨基吡啶的正性肌力作用支持了I-Ca、I-L的间接增加，但对心房制剂中的I-Ca、I-L没有直接影响，而对心室制剂没有影响。与模型预测一致，E-4031阻断I-Kr将SR中I-Kur阻断的APD缩短效应转化为AP延长效应。结论-抑制I-Kur是否延长或缩短APD取决于心房的疾病状态，并由电重构水平决定。
Background - The ultrarapid outward current I-Kur is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias. The effects of selective block of I-Kur by low concentrations of 4-aminopyridine or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials (APs) in trabeculae from patients in sinus rhythm (SR) or chronic atrial fibrillation (AF).Methods and Results - AP duration at 90% repolarization (APD(90)) was shorter in AF than in SR (300 +/- 16 ms, n = 6, versus 414 +/- 10 ms, n = 15), whereas APD(20) was longer ( 35 +/- 9 ms in AF versus 5 +/- 2 ms in SR, P < 0.05). 4-Aminopyridine ( 5 μmol/L) elevated the plateau to more positive potentials from - 21 +/- 3 to - 6 +/- 3 mV in SR and 0 +/- 3 to + 12 +/- 3 mV in AF. 4-Aminopyridine reversibly shortened APD(90) from 414 +/- 10 to 350 +/- 10 ms in SR but prolonged APD(90) from 300 +/- 16 to 320 +/- 13 ms in AF. Similar results were obtained with AVE 0118 (6 μmol/L). Computer simulations of I-Kur block in human atrial APs predicted secondary increases in I-Ca,I-L and in the outward rectifiers I-Kr and I-Ks, with smaller changes in AF than SR. The indirect increase in I-Ca,I-L was supported by a positive inotropic effect of 4-aminopyridine without direct effects on I-Ca,I-L in atrial but not ventricular preparations. In accordance with the model predictions, block of I-Kr with E-4031 converted APD shortening effects of I-Kur block in SR into AP prolongation.Conclusions - Whether inhibition of I-Kur prolongs or shortens APD depends on the disease status of the atria and is determined by the level of electrical remodeling.