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神经元Kv4通道复合体。

The neuronal Kv4 channel complex.

作者信息

Covarrubias Manuel, Bhattacharji Aditya, De Santiago-Castillo Jose A, Dougherty Kevin, Kaulin Yuri A, Na-Phuket Thanawath Ratanadilok, Wang Guangyu

机构信息

Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College of Thomas Jefferson University, 1020 Locust Street, JAH 245, Philadelphia, PA 19107, USA.

出版信息

Neurochem Res. 2008 Aug;33(8):1558-67. doi: 10.1007/s11064-008-9650-8. Epub 2008 Mar 21.

Abstract

Kv4 channel complexes mediate the neuronal somatodendritic A-type K(+) current (I(SA)), which plays pivotal roles in dendritic signal integration. These complexes are composed of pore-forming voltage-gated alpha-subunits (Shal/Kv4) and at least two classes of auxiliary beta-subunits: KChIPs (K(+)-Channel-Interacting-Proteins) and DPLPs (Dipeptidyl-Peptidase-Like-Proteins). Here, we review our investigations of Kv4 gating mechanisms and functional remodeling by specific auxiliary beta-subunits. Namely, we have concluded that: (1) the Kv4 channel complex employs novel alternative mechanisms of closed-state inactivation; (2) the intracellular Zn(2+) site in the T1 domain undergoes a conformational change tightly coupled to voltage-dependent gating and is targeted by nitrosative modulation; and (3) discrete and specific interactions mediate the effects of KChIPs and DPLPs on activation, inactivation and permeation of Kv4 channels. These studies are shedding new light on the molecular bases of I(SA) function and regulation.

摘要

Kv4通道复合物介导神经元胞体树突状A 型钾电流(I(SA)),该电流在树突信号整合中起关键作用。这些复合物由形成孔道的电压门控α亚基(Shal/Kv4)和至少两类辅助β亚基组成:钾通道相互作用蛋白(KChIPs)和类二肽基肽酶蛋白(DPLPs)。在此,我们回顾我们对Kv4门控机制以及特定辅助β亚基对其功能重塑的研究。具体而言,我们得出以下结论:(1)Kv4通道复合物采用新型的关闭状态失活替代机制;(2)T1结构域中的细胞内锌离子位点发生与电压依赖性门控紧密偶联的构象变化,并受到亚硝化调节的作用;(3)离散且特定的相互作用介导KChIPs和DPLPs对Kv4通道激活、失活和通透的影响。这些研究为I(SA)功能和调节的分子基础提供了新的见解。

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