The Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) and Epilepsy.
The Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) and Epilepsy.
复制标题
DOI：
10.2174/1871527317666180404104055
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Kaikai Zang;Yuwen Zhang;Jie Hu;Yun Wang
中科院分区：
文献类型：
--
作者：
Kaikai Zang;Yuwen Zhang;Jie Hu;Yun Wang
背景与目的大电导、钙离子和电压激活的钾离子通道（BK）是广泛分布于哺乳动物细胞中的一种通道蛋白，其功能是影响细胞膜兴奋性和Ca ~（2+）信号转导。BK通道可被神经元兴奋引起的细胞内Ca ~（2+）浓度升高激活，然后终止动作电位并向外释放K ~+。此外，BK通道诱导的后超极化关闭Cav通道，从而阻止过量的Ca 2+内流。考虑到这种负反馈效应，BK通道的作用是降低膜兴奋性，以防止过度兴奋，这是癫痫的典型特征。因此，可以合理地假设，当BK通道活性降低时，膜兴奋性将增加。然而，当BK通道功能处于上调或下调状态时，膜兴奋性均表现为升高。改变BK通道活性的因素，如基因突变、多态性、导致功能丧失或获得的通道开放剂或阻断剂，都与癫痫发作有关。结论本文综述了BK通道的分子特性、信号复合物和通道功能障碍的研究进展，并重点介绍了BK通道与癫痫病理生理的关系。
BACKGROUND & OBJECTIVE The large conductance, calcium- and voltage-activated potassium channels (BK) are widely distributed channel proteins which exist in virtually every cell type of mammals and function to influence membrane excitability and Ca2+ signaling. BK channels can be activated by the increase of the intracellular Ca2+ concentration, a consequence of neuronal excitation, and then terminate the action potential with the outward K+ flux. Moreover, after-hyperpolarization induced by BK channels closes Cav channels and thus precludes excessive Ca2+ influx. Considering this negative feedback effect, BK channel seemly acts to decrease membrane excitability in order to prevent hyperexcitation which is a typical characteristic of epilepsy. Therefore, one may reasonably suppose that membrane excitability would increase when the BK channel activity decreases. However, the membrane excitability displays elevation when the function of BK channel is under either upregulated or down-regulated status. Factors altering the activity of BK channels, such as gene mutations, polymorphism, channel openers or blockers that lead to loss- or gain-of-function, have all been linked to epilepsy onset. CONCLUSION The aim of this review is to summarize existing knowledge and recent findings on the molecular properties, signaling complex and channel dysfunction of the BK channels with a particular attention to the possible relevance to the pathophysiology of epilepsy.