Kv7 K+ Channels in Airway Smooth Muscle Cells as Target for Asthma Therapy

Airway hyperresponsiveness (AHR) is an important etiological feature of asthma, the molecular mechanisms of which are poorly understood, thus preventing development of specific and effective therapies. We investigate the role played by Kv7 voltage-activated potassium channels in the pathophysiology of AHR and evaluate the significance of their regulation in treatment of asthma. Our studies provide the first evidence for expression of multiple Kv7 channels in guinea pig and human airways and demonstrate that the expression of Kv7 channels is reduced in allergen-sensitized guinea pig airways. Our ex vivo functional studies reveal that clinically available Kv7 channel activators attenuate the bronchoconstrictor agonists mediated airway constriction. This protective effect is likely due to the increase in the activity of remaining Kv7 channels in allergen-sensitized airways, thereby improving control on membrane polarization. These findings highlight a potential therapeutic strategy for regulation of airway diameter in the treatment of asthma and other airway diseases