Potassium Channels of the Airway Epithelium

Maintenance of potassium (K⁺) homeostasis across cell membranes is essential for life. While systemic K⁺ balance is primarily regulated by the kidneys and intestines, ion channels, pumps, and transporters govern K⁺ movement across epithelial barriers at the cellular level. Despite the prevalence of diseases caused by disrupted K⁺ homeostasis, the role of K⁺ channels in the lungs has received comparatively little attention. The airway epithelium expresses a diverse array of K⁺ channels that regulate key functions such as transepithelial ion transport, ciliary beating, and mucus secretion. These processes are fundamental components of mucociliary clearance (MCC), the primary innate defense mechanism of the lungs. Dysfunction of MCC is central to muco-obstructive diseases, including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma. While K⁺ channels were once considered therapeutic targets for enhancing anion secretion in CF, initial interest waned. However, it has been reinvigorated by recent findings showing that drugs targeting CFTR can also modulate airway epithelial K⁺ channels and facilitate MCC. In this review, we compile current evidence on targeting K⁺ channels to treat muco-obstructive diseases. We discuss therapeutic opportunities offered by K⁺ channel modulators, highlight emerging functions of these channels in the airways, and outline priorities for future research.