Department of Neurology and Epileptology, Center for Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Pflugers Arch. 2010 Jul;460(2):277-88. doi: 10.1007/s00424-010-0831-3. Epub 2010 Apr 18.
KV7 voltage-gated potassium channels, encoded by the KCNQ gene family, have caught increasing interest of the scientific community for their important physiological roles, which are emphasized by the fact that four of the five so far identified members are related to different hereditary diseases. Furthermore, these channels prove to be attractive pharmacological targets for treating diseases characterized by membrane hyperexcitability. KV7 channels are expressed in brain, heart, thyroid gland, pancreas, inner ear, muscle, stomach, and intestines. They give rise to functionally important potassium currents, reduction of which results in pathologies such as long QT syndrome, diabetes, neonatal epilepsy, neuromyotonia, or progressive deafness. Here, we summarize some key traits of KV7 channels and review how their molecular deficiencies could explain diverse disease phenotypes. We also assess the therapeutic potential of KV7 channels; in particular, how the activation of KV7 channels by the compounds retigabine and R-L3 may be useful for treatment of epilepsy or cardiac arrhythmia.
KV7 电压门控钾通道由 KCNQ 基因家族编码，由于其重要的生理作用，越来越引起科学界的关注，事实上，迄今为止已鉴定的五个成员中的四个与不同的遗传性疾病有关。此外，这些通道被证明是治疗以膜过度兴奋为特征的疾病的有吸引力的药理学靶点。KV7 通道在脑、心脏、甲状腺、胰腺、内耳、肌肉、胃和肠道中表达。它们产生功能上重要的钾电流，其减少导致长 QT 综合征、糖尿病、新生儿癫痫、肌强直性神经病或进行性耳聋等病理。在这里，我们总结了 KV7 通道的一些关键特征，并回顾了其分子缺陷如何解释不同的疾病表型。我们还评估了 KV7 通道的治疗潜力；特别是，化合物 retigabine 和 R-L3 通过激活 KV7 通道如何有助于治疗癫痫或心律失常。
