Department of Molecular Pharmacology & Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
Department of Molecular Pharmacology & Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
Pharmacol Ther. 2016 Sep;165:14-25. doi: 10.1016/j.pharmthera.2016.05.002. Epub 2016 May 11.
Smooth muscle cells provide crucial contractile functions in visceral, vascular, and lung tissues. The contractile state of smooth muscle is largely determined by their electrical excitability, which is in turn influenced by the activity of potassium channels. The activity of potassium channels sustains smooth muscle cell membrane hyperpolarization, reducing cellular excitability and thereby promoting smooth muscle relaxation. Research over the past decade has indicated an important role for Kv7 (KCNQ) voltage-gated potassium channels in the regulation of the excitability of smooth muscle cells. Expression of multiple Kv7 channel subtypes has been demonstrated in smooth muscle cells from viscera (gastrointestinal, bladder, myometrial), from the systemic and pulmonary vasculature, and from the airways of the lung, from multiple species, including humans. A number of clinically used drugs, some of which were developed to target Kv7 channels in other tissues, have been found to exert robust effects on smooth muscle Kv7 channels. Functional studies have indicated that Kv7 channel activators and inhibitors have the ability to relax and contact smooth muscle preparations, respectively, suggesting a wide range of novel applications for the pharmacological tool set. This review summarizes recent findings regarding the physiological functions of Kv7 channels in smooth muscle, and highlights potential therapeutic applications based on pharmacological targeting of smooth muscle Kv7 channels throughout the body.
平滑肌细胞在内脏、血管和肺部组织中提供关键的收缩功能。平滑肌的收缩状态在很大程度上取决于其电兴奋性，而钾通道的活性又反过来影响平滑肌的兴奋性。钾通道的活性维持平滑肌细胞膜超极化，降低细胞兴奋性，从而促进平滑肌松弛。过去十年的研究表明，Kv7（KCNQ）电压门控钾通道在调节平滑肌细胞的兴奋性方面起着重要作用。已经在来自内脏（胃肠道、膀胱、子宫肌）、全身和肺血管以及来自包括人类在内的多种物种的肺气道的平滑肌细胞中证明了多种 Kv7 通道亚型的表达。一些已被临床使用的药物，其中一些是为了针对其他组织中的 Kv7 通道而开发的，已被发现对平滑肌 Kv7 通道具有强大的作用。功能研究表明，Kv7 通道激活剂和抑制剂分别具有使平滑肌松弛和收缩的能力，这表明该药理学工具集具有广泛的新型应用。这篇综述总结了 Kv7 通道在平滑肌中的生理功能的最新发现，并强调了基于全身平滑肌 Kv7 通道的药理学靶向的潜在治疗应用。
