Function and mechanism of axonal targeting of voltage-sensitive potassium channels.
Function and mechanism of axonal targeting of voltage-sensitive potassium channels.
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DOI：
10.1016/j.pneurobio.2011.04.009
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发表时间：
2011-07
影响因子：
6.7
通讯作者：
Barry J
中科院分区：
文献类型：
--
作者：
Gu C;Barry J
将各种离子通道精确定位到适当的亚细胞区室对于神经元的兴奋性和突触传递至关重要。通过膜电位的去极化激活的轴突K+通道参与动作电位的复极化阶段，并因此调节编码输出信号的动作电位放电模式。此外，这些通道中的一些可以直接控制神经递质释放轴突末梢通过限制局部膜兴奋性和限制Ca 2+内流。K+通道不仅在生物物理学和药理学性质上不同，而且在表达和亚细胞分布上也不同。重要的是，通道蛋白的适当靶向是轴突的电和化学功能的先决条件。在这篇综述中，我们首先强调最近的研究表明，轴突K+通道在轴突兴奋性的局部调节中的不同作用。接下来，我们将重点介绍轴突靶向基序和轴突中几种不同类型的K+通道机制的研究进展。调节K+通道的靶向和活性可能是一种新形式的神经元可塑性的基础。这一研究领域可以通过操纵神经元兴奋性来治疗神经系统疾病，如多发性硬化症、神经性疼痛和阿尔茨海默病，从而有助于产生新的治疗策略。
Precise localization of various ion channels into proper subcellular compartments is crucial for neuronal excitability and synaptic transmission. Axonal K+ channels that are activated by depolarization of the membrane potential participate in the repolarizing phase of the action potential, and hence regulate action potential firing patterns, which encode output signals. Moreover, some of these channels can directly control neurotransmitter release at axonal terminals by constraining local membrane excitability and limiting Ca2+ influx. K+ channels differ not only in biophysical and pharmacological properties, but in expression and subcellular distribution as well. Importantly, proper targeting of channel proteins is a prerequisite for electrical and chemical functions of axons. In this review, we first highlight recent studies that demonstrate different roles of axonal K+ channels in the local regulation of axonal excitability. Next, we focus on research progress in identifying axonal targeting motifs and machinery of several different types of K+ channels present in axons. Regulation of K+ channel targeting and activity may underlie a novel form of neuronal plasticity. This research field can contribute to generating novel therapeutic strategies through manipulating neuronal excitability in treating neurological diseases, such as multiple sclerosis, neuropathic pain, and Alzheimer’s disease.
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DOI：
10.1111/j.1460-9568.2010.07447.x
发表时间：
2010-11
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Barry J;Gu Y;Gu C
通讯作者：
Gu C
DOI：
10.1083/jcb.200805169
发表时间：
2008-12-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bréchet A;Fache MP;Brachet A;Ferracci G;Baude A;Irondelle M;Pereira S;Leterrier C;Dargent B
通讯作者：
Dargent B
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW
影响因子：
56.9
作者：
Asbury, CL;Fehr, AN;Block, SM
通讯作者：
Block, SM
影响因子：
5.3
作者：
Berkefeld, Henrike;Fakler, Bernd
通讯作者：
Fakler, Bernd