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SCREENING METHOD FOR ION CHANNEL MODULATORS USING MUTATED BKCA CHANNEL

机译:突变BKCA通道的离子通道调制器筛选方法

摘要

The present disclosure relates to a doubly mutated BKCa channel construct and a novel cell-based screening system for ion channel modulators using the same. A doubly mutated BKCa channel-comprising cell-based system of the present invention, when compared to a control group, shows remarkably increased fluorescence caused by membrane depolarization, regardless of whether there is a separate increase of [Ca2+]i, and shows activity (movement in the negative direction of a G/V curve) that is further triggered by a known activator (for example, CTBIC). Therefore, the system of the present disclosure is capable of more effectively and accurately analyzing the activity of an ion channel, and thus can be effectively applied not only to the separation/identification of ion channel modulators but also to screening for a therapeutic agent for a condition, disease or disorder related to the modulation of a BKCa channel.
机译:本公开涉及双突变的BK Ca 通道构建体和使用其的用于离子通道调节剂的新颖的基于细胞的筛选系统。与对照组相比,本发明的包含双突变的包含BK Ca 通道的细胞的系统与对照组相比,显示出由膜去极化引起的荧光显着增加,而与[[ Ca 2 + ] i ,并显示由已知激活剂(例如CTBIC)进一步触发的活性(G / V曲线的负方向移动) 。因此,本公开的系统能够更有效和准确地分析离子通道的活性,因此不仅可以有效地应用于离子通道调节剂的分离/鉴定,而且可以有效地用于筛选治疗药物。与BK Ca 通道的调节有关的疾病,疾病或障碍。

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