The present disclosure relates to methods and compositions for modulating the activity of KCNQ channels as a means for reducing the effects of aberrant KCNQ channel function associated with epilepsy, deafness and arrhythmias including but not limited to, Long-QT syndrome (“LQTS”), and atrial fibrillation. The present disclosure also relates to the discovery of certain regions of KCNQ channels that interact with various channel stimulating molecules such as, ATP, and PIP2, as well as KCNQ channel domains that effect voltage dependant channel activation. The disclosure is also directed to the use of small molecules to modulate KCNQ channel activity in a cell. Moreover, the present disclosure relates to the therapeutic effects of treating a subject with modulators of KCNQ channel activity.
本公开涉及调节 KCNQ 通道活性的方法和组合物,以此减少与癫痫、耳聋和心律失常(包括但不限于长 QT 综合征("LQ
TS")和心房颤动)相关的 KCNQ 通道功能异常的影响。本公开内容还涉及发现 KCNQ 通道的某些区域与各种通道刺激分子(如
ATP 和
PIP2)相互作用,以及影响电压依赖性通道激活的 KCNQ 通道结构域。本公开还涉及使用小分子来调节细胞中 KCNQ 通道的活性。此外,本公开还涉及用 KCNQ 通道活性调节剂治疗受试者的治疗效果。