Differential inhibition of transient outward currents of Kv1.4 and Kv4.3 by endothelin
Differential inhibition of transient outward currents of Kv1.4 and Kv4.3 by endothelin
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DOI：
10.1016/j.bbrc.2003.09.062
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发表时间：
2003-10-17
影响因子：
3.1
通讯作者：
Yanagisawa, T
中科院分区：
文献类型：
--
作者：
Hagiwara, K;Nunoki, K;Yanagisawa, T
比较了内皮素对爪蟾卵母细胞表达系统Kv1.4和Kv4.3通道瞬时外向钾电流的影响。刺激与钾通道共表达的内皮素受体ETA可使两种瞬时外向钾电流均降低。10（-8）M ET-1使Kv1.4瞬时外向电流下降约85%，使Kv4.3瞬时外向电流下降约60%。通过诱变实验，我们确定了两个磷酸化位点的PKC和CaMK Ⅱ在Kv1.4负责减少I-到ET-1。在Kv4.3中，确定了PKC磷酸化位点，其部分负责I-to的减少。I-to抑制的差异可以归因于细胞内信号传导的差异，包括磷酸化位点的数量。这些结果为进一步了解心力衰竭时室性心律失常的分子机制提供了线索，内皮素参与了心力衰竭时室性心律失常的发病过程。(C)2003年爱思唯尔公司All rights reserved.
The effects of endothelin on the transient outward K+ currents were compared between Kv1.4 and Kv4.3 channels in Xenopus oocytes expression system. Both transient outward K+ Currents were decreased by stimulation of endothelin receptor ETA coexpressed with the K+ channels. Transient outward current of Kv1.4 was decreased by about 85% after 10(-8) M ET-1, while that of Kv4.3 was decreased by about 60%. By mutagenesis experiments we identified two phosphorylation sites of PKC and CaMKII in Kv1.4 responsible for the decrease in I-to by ET-1. In Kv4.3 a PKC phosphorylation site was identified which is in part responsible for the decrease in I-to. Differences in the suppression of I-to could be ascribed to the difference in intracellular signaling including the number of phosphorylation sites. These findings might give clues for the understanding of molecular mechanism of ventricular arrhythmias in heart failure, in which endothelin is involved in the pathogenesis. (C) 2003 Elsevier Inc. All rights reserved.