Novel treatment strategies for smooth muscle disorders: Targeting Kv7 potassium channels

• Published in: Pharmacology & therapeutics (Oxford) 2016-09, Vol.165, p.14-25
• Main Authors: Haick, Jennifer M, Byron, Kenneth L
• Format: Article
• Language: English
• Subjects: Animals; Bronchoconstriction - drug effects; Bronchoconstrictor Agents - therapeutic use; Bronchodilator Agents - therapeutic use; Drug Design; Humans; KCNQ Potassium Channels - agonists; KCNQ Potassium Channels - antagonists & inhibitors; KCNQ Potassium Channels - metabolism; Molecular Targeted Therapy; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Muscle, Smooth - physiopathology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiopathology; Potassium Channel Blockers - adverse effects; Potassium Channel Blockers - therapeutic use; Respiratory System - drug effects; Respiratory System - metabolism; Respiratory System - physiopathology; Signal Transduction - drug effects; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Viscera - drug effects; Viscera - metabolism; Viscera - physiopathology
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2016.05.002

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.