KChAP/Kvβ1.2 interactions and their effects on cardiac Kv channel expression

KChAP/Kvβ1.2 interactions and their effects on cardiac Kv channel expression
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DOI:
10.1152/ajpcell.2001.281.1.c290
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发表时间:
2001-07-01
影响因子:
5.5
通讯作者:
Brown, AM
Brown, AM
中科院分区:
生物学2区
文献类型:
--
作者:
Kuryshev, YA;Wible, BA;Brown, AM

文献摘要

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KChAP和电压依赖性K+(Kv)β亚基是与Kv通道相互作用的两种不同类型的细胞质蛋白。KChAP充当Kv2.1和Kv4.3通道的伴侣。它也与Kv1.x通道结合,但除Kv1.3外,不增加Kv1.x电流。Kv β亚基与Kv1.x通道组装;它们表现出“伴侣样”行为并改变门控特性。此外,KChAP和Kv β亚基相互作用。在这里,我们研究的后果,这种相互作用的Kv电流在非洲爪蟾卵母细胞注射不同组合的cRNA,包括Kv β 1.2,KChAP,无论是Kv1.4,Kv1.5,Kv2.1,或Kv4.3。我们发现,KChAP减弱了Kvb1.2产生的Kv1.5电流的抑制,Kvb1.2消除了KChAP产生的Kv2.1和Kv4.3电流的增加。KChAP和Kvb1.2都在心肌细胞中表达,其中Kv1.5和Kv2.1产生持续的外向电流,Kv4.3和Kv1.4产生瞬时外向电流。因为它们相互作用,KChAP或Kvb1.2可能会改变持续和短暂的心脏Kv电流。这两种不同类型的调节蛋白的相互作用可能构成一种新的机制,调节心脏K+电流。
KChAP and voltage-dependent K+ (Kv) beta -subunits are two different types of cytoplasmic proteins that interact with Kv channels. KChAP acts as a chaperone for Kv2.1 and Kv4.3 channels. It also binds to Kv1.x channels but, with the exception of Kv1.3, does not increase Kv1.x currents. Kv beta -subunits are assembled with Kv1.x channels; they exhibit "chaperone-like" behavior and change gating properties. In addition, KChAP and Kv beta -subunits interact with each other. Here we examine the consequences of this interaction on Kv currents in Xenopus oocytes injected with different combinations of cRNAs, including Kv beta1.2, KChAP, and either Kv1.4, Kv1.5, Kv2.1, or Kv4.3. We found that KChAP attenuated the depression of Kv1.5 currents produced by Kvb1.2, and Kvb1.2 eliminated the increase of Kv2.1 and Kv4.3 currents produced by KChAP. Both KChAP and Kvb1.2 are expressed in cardiomyocytes, where Kv1.5 and Kv2.1 produce sustained outward currents and Kv4.3 and Kv1.4 generate transient outward currents. Because they interact, either KChAP or Kvb1.2 may alter both sustained and transient cardiac Kv currents. The interaction of these two different classes of modulatory proteins may constitute a novel mechanism for regulating cardiac K+ currents.