Wang Jing-jing, Li Yang
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai 201203, China.
Acta Pharmacol Sin. 2016 Jan;37(1):25-33. doi: 10.1038/aps.2015.131. Epub 2015 Dec 21.
M channels, an important regulator of neural excitability, are composed of four subunits of the Kv7 (KCNQ) K(+) channel family. M channels were named as such because their activity was suppressed by stimulation of muscarinic acetylcholine receptors. These channels are of particular interest because they are activated at the subthreshold membrane potentials. Furthermore, neural KCNQ channels are drug targets for the treatments of epilepsy and a variety of neurological disorders, including chronic and neuropathic pain, deafness, and mental illness. This review will update readers on the roles of KCNQ channels in the sensory system and neural circuits as well as discuss their respective mechanisms and the implications for physiology and medicine. We will also consider future perspectives and the development of additional pharmacological models, such as seizure, stroke, pain and mental illness, which work in combination with drug-design targeting of KCNQ channels. These models will hopefully deepen our understanding of KCNQ channels and provide general therapeutic prospects of related channelopathies.
M通道是神经兴奋性的重要调节因子,由Kv7(KCNQ)钾通道家族的四个亚基组成。M通道之所以如此命名,是因为它们的活性受到毒蕈碱型乙酰胆碱受体刺激的抑制。这些通道特别引人关注,因为它们在阈下膜电位时被激活。此外,神经KCNQ通道是治疗癫痫和多种神经系统疾病(包括慢性疼痛和神经性疼痛、耳聋及精神疾病)的药物靶点。本综述将向读者介绍KCNQ通道在感觉系统和神经回路中的作用,同时讨论其各自的机制以及对生理学和医学的意义。我们还将考虑未来的研究方向以及其他药理学模型的发展,如癫痫、中风、疼痛和精神疾病等,这些模型与针对KCNQ通道的药物设计相结合。有望通过这些模型加深我们对KCNQ通道的理解,并为相关通道病提供总体治疗前景。