Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene encoding the chloride channel “cystic
fibrosis transmembrane conductance regulator” (CFTR). The lack of functional CFTR in CF airways leads to impaired
ion and fluid homeostasis of the fluid layer which lines the airway surfaces (ASL). The ASL is important for proper ciliary
beat and clearance of mucus from the airways. According to the “low volume hypothesis”, CF airway epithelia hyperabsorb
sodium via the epithelial sodium channel (ENaC). Although the contribution of ENaC to CF pathogenesis is still
under debate, there is convincing data demonstrating that re-hydration of the ASL might improve mucociliary clearance in
CF patients. ASL re-hydration might, amongst other things, be achieved by a block of airway transepithelial sodium absorption
with inhibitors of ENaC. This mini-review article describes the role of ENaC in ASL fluid homeostasis and rehydration,
and summarizes the current state of the art in the discovery and establishment of compounds which inhibit
ENaC activity and may represent pharmacological tools for the treatment of CF.
Keywords: Airway surface liquid, amiloride, CFTR, cystic fibrosis, ENaC, inhibitor, sodium transport.
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