Department of Neurology, Institutes of Brain Science, State Key Laboratory for Medical Neurobiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Neurosurgery, Jingan Hospital, Fudan University, Shanghai, China.
CNS Neurol Disord Drug Targets. 2018;17(4):248-254. doi: 10.2174/1871527317666180404104055.
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.
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.
大电导、钙激活和电压门控钾通道（BK）是广泛分布的通道蛋白，存在于哺乳动物的几乎所有细胞类型中，其功能是影响膜兴奋性和 Ca2+信号转导。BK 通道可被胞内 Ca2+浓度的增加激活，这是神经元兴奋的结果，然后通过外向 K+流终止动作电位。此外，BK 通道诱导的超极化后关闭 Cav 通道，从而防止过多的 Ca2+内流。鉴于这种负反馈效应，BK 通道似乎通过降低膜兴奋性来防止过度兴奋，而过度兴奋是癫痫的典型特征。因此，人们可能会合理地假设，当 BK 通道活性降低时，膜兴奋性会增加。然而，当 BK 通道的功能处于上调或下调状态时，膜兴奋性会升高。改变 BK 通道活性的因素，如基因突变、多态性、通道开放剂或阻滞剂导致功能丧失或获得，都与癫痫发作有关。
本综述的目的是总结 BK 通道的分子特性、信号复合物和通道功能障碍的现有知识和最新发现，特别关注其与癫痫病理生理学的可能相关性。
