ICaL and Ito mediate rate-dependent repolarization in rabbit atrial myocytes
ICaL and Ito mediate rate-dependent repolarization in rabbit atrial myocytes
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I-CaL 和 I-介导兔心房肌细胞的速率依赖性复极
DOI：
10.1007/s13105-017-0603-z
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发表时间：
2018-02-01
影响因子：
3.4
通讯作者：
Li, Yi-Gang
中科院分区：
文献类型：
--
作者：
Hou, Jian-Wen;Li, Wei;Li, Yi-Gang
心肌细胞动作电位（AP）的速率依赖性复极化（RDR）在心律失常的发生中起着至关重要的作用，心房RDR与房颤有关。然而，关于RDR在兔心房中的作用的详细研究很少。本研究从家兔心脏中分离心房细胞，探讨单个心房细胞的速率依赖特性，以阐明其潜在的机制。结果表明，在控制条件下，20%复极（APD20）和50%复极（APD50）动作电位持续时间的速率依赖性延长明显，而90%复极（APD90）动作电位持续时间的速率依赖性延长不明显。使用瞬时外向钾电流（I-to）抑制剂4-氨基吡啶（4-AP, 2 mM）可有效消除APD20和APD50的变化，并揭示了APD90的速率依赖性降低，进一步添加l型钙电流（I-CaL）抑制剂硝苯地平（30 μ M）可减少APD90。然而，使用选择性晚钠电流（I-NaL）抑制剂GS-458967 （GS967, 1 μ M）对心房细胞APD90的影响很小，无论4-AP存在与否。与ap的结果一致，I-to和I-CaL表现出显著的速率依赖性降低，因为它们的再激活动力学缓慢。此外，兔心房I-NaL的幅度很小，其速率依赖性变化可以忽略不计。综上所述，我们的研究表明，I-to和I-CaL介导了兔心房AP的RDR，而I-NaL的影响很小。
Rate-dependent repolarization (RDR) of action potential (AP) in cardiomyocyte plays a critical role in the genesis of arrhythmias and RDR in atrium has been linked with atrial fibrillation. However, detailed studies focusing on the role of RDR in rabbit atrium are scant. In this study, atrial cells were isolated from rabbit heart and rate-dependent property was explored in single atrial cell to elucidate the underlying mechanism. Our results indicated that rate-dependent prolongation was evident at the action potential duration at 20% (APD20) and 50% (APD50) repolarization but not at 90% repolarization (APD90) under control condition. Using transient outward potassium current (I-to) inhibitor 4-Aminopyridine (4-AP, 2 mM) effectively eliminated the changes in APD20 and APD50, and unmasked the rate-dependent reduction of APD90 which could be diminished by further adding L-type calcium current (I-CaL) inhibitor nifedipine (30 mu M). However, using the selective late sodium current (I-NaL) inhibitor GS-458967 (GS967, 1 mu M) caused minimal effect on APD90 of atrial cells both in the absence and presence of 4-AP. In consistence with results from APs, I-to and I-CaL displayed significant rate-dependent reduction because of their slow reactivation kinetics. In addition, the magnitude of I-NaL in rabbit atrium was so small that its rate-dependent changes were negligible. In conclusion, our study demonstrated that I-to and I-CaL mediate RDR of AP in rabbit atrium, while minimal effect of I-NaL was seen.