Airway epithelial ion transport

Airway epithelial ion transport is a coordinated physiological process responsible for maintaining the volume, composition, and pH of the airway surface liquid (ASL), which is essential for effective mucociliary clearance and lung defense [2, 5, 14]. This system involves a variety of ion channels and transporters, most notably the cystic fibrosis transmembrane conductance regulator (CFTR) for chloride and bicarbonate secretion, and the epithelial sodium channel (ENaC) for sodium absorption [7, 14, 16]. In diseases like cystic fibrosis, mutations in CFTR lead to defective anion secretion and unregulated sodium hyperabsorption, resulting in ASL dehydration, thick mucus, and chronic infection [7, 13, 16]. Therapeutic strategies target this system through CFTR modulators, such as potentiators and correctors, to restore channel function, or ENaC inhibitors to prevent excessive fluid absorption [10, 11, 15]. Other components like TMEM16A and SLC26A9 are also being explored as alternative targets to bypass CFTR defects and rehydrate the airways [9, 11, 15]. Proper regulation of these transport mechanisms is vital for preventing the progression of chronic obstructive pulmonary disease (COPD) and other respiratory conditions [3, 13].

Other names

Airway surface liquid regulationEpithelial ion transportMucociliary clearance regulationRespiratory epithelial ion transport

Modulation of airway epithelial ion transport involves CFTR potentiation and correction to restore chloride and bicarbonate secretion [11, 15], ENaC inhibition to block excessive sodium and water reabsorption [8, 15], activation of purinergic receptors (e.g., P2Y2) to stimulate alternative chloride channels [12], or the use of osmotic agents to directly hydrate the airway surface liquid [11].