Contribution of I Kr and I K1 to ventricular repolarization in canine and human myocytes: is there any influence of action potential duration?
Contribution of I Kr and I K1 to ventricular repolarization in canine and human myocytes: is there any influence of action potential duration?
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DOI：
10.1007/s00395-008-0730-3
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发表时间：
2009-01-01
影响因子：
9.5
通讯作者：
Nanasi, Peter P.
中科院分区：
文献类型：
--
作者：
Jost, Norbert;Acsai, Karoly;Nanasi, Peter P.
本研究的目的是研究快速延迟整流钾电流（I (Kr)）和内向整流钾电流（I (K1)）在心室复极期间的分布，作为动作电位持续时间和复极速率的函数。采用膜片钳技术的全细胞结构监测I （Kr）和I （K1）在动作电位平台期和终末复极期。以不同周期长度（0.4 ~ 5 s）记录的动作电位和不同斜率（0.5 ~ 3 V/s）的复极化电压坡道作为指令信号。I （Kr）和I （K1）分别被E-4031和BaCl2分解为差分电流。犬动作电位平台期记录的I （Kr）和I （K1）的峰值幅值和平均值不受动作电位持续时间的影响。在终末复极化期间，I （Kr）和I （K1）达到峰值的膜电位也与动作电位持续时间无关。在未患病的人心室肌细胞和犬细胞中，当使用不同坡度的复极电压诱发I （Kr）和I （K1）时，也得到了类似的结果。动作电位箝位实验表明，在0.4 s和5 s范围内，终端复极过程中I （Kr）、I （K1）和净向外电流的峰值与起搏周期长度无关。结果表明，在狗和人的心室动作电位期间，动作电位的配置不影响I （Kr）和I （K1）的振幅，这表明动作电位持续时间的速率依赖性变化不太可能与这些物种中I （Kr）或I （K1）动力学的速率依赖性改变有关。
The aim of the present work was to study the profile of the rapid delayed rectifier potassium current (I (Kr)) and the inward rectifier potassium current (I (K1)) during ventricular repolarization as a function of action potential duration and rate of repolarization.Whole cell configuration of the patch clamp technique was used to monitor I (Kr) and I (K1) during the action potential plateau and terminal repolarization. Action potentials recorded at various cycle lengths (0.4-5 s) and repolarizing voltage ramps having various slopes (0.5-3 V/s) were used as command signals. I (Kr) and I (K1) were identified as difference currents dissected by E-4031 and BaCl2, respectively.Neither peak amplitudes nor mean values of I (Kr) and I (K1) recorded during the plateau of canine action potentials were influenced by action potential duration. The membrane potential where I (Kr) and I (K1) peaked during the terminal repolarization was also independent of action potential duration. Similar results were obtained in undiseased human ventricular myocytes, and also in canine cells when I (Kr) and I (K1) were evoked using repolarizing voltage ramps of various slopes. Action potential voltage clamp experiments revealed that the peak values of I (Kr), I (K1), and net outward current during the terminal repolarization were independent of the pacing cycle length within the range of 0.4 and 5 s.The results indicate that action potential configuration fails to influence the amplitude of I (Kr) and I (K1) during the ventricular action potential in dogs and humans, suggesting that rate-dependent changes in action potential duration are not likely related to rate-dependent alterations in I (Kr) or I (K1) kinetics in these species.