Function and pharmacology of human Na+-activated K+ channels

人类KCNT1基因编码松弛的Na+激活K+通道，它的遗传和自发功能获得突变最近被认为与严重和耐药癫痫有关。患有这些疾病的儿童生活质量很差，许多人活不到成年。因此，用有效和选择性的小分子疗法抑制这一通道是治疗这些癫痫的优先策略。SLACK通道是一种研究和了解很少的钾通道，利兹小组是少数几个在研究其功能、药理学和突变的影响方面有经验的实验室之一。基础研究需要了解(A)癫痫相关突变究竟如何影响通道的结构和功能，以及(B)已知的抑制剂和激动剂发挥作用的机制。

Inherited and spontaneous gain-of-function mutations in the human KCNT1 gene, which encodes the SLACK Na+-activated K+ channel, have recently been linked to severe and drug-resistant epilepsies. Children suffering from these disorders have poor quality of life and many do not survive to adulthood. Inhibiting this channel with a potent and selective small molecule therapeutic is therefore a prioritised strategy for the treatment of these epilepsies. The SLACK channel is a poorly studied and understood potassium channel, with the Leeds group one of only a handful of laboratories with experience in studying its function, pharmacology, and effects of mutations. Underpinning fundamental research is required to understand (a) how exactly the epilepsy-related mutations affect both the structure and function of the channel, and (b) the mechanism by which known inhibitors and activators exert their effects.