Cystic fibrosis transmembrane conductance regulator and epithelial sodium channel (CFTR and ENaC)

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and the Epithelial Sodium Channel (ENaC) are integral membrane proteins that maintain ion and fluid homeostasis across epithelial surfaces, particularly in the lungs and gastrointestinal tract (UniProt P13569, P37088). CFTR functions as a cAMP-activated chloride channel and a regulator of other ion channels, most notably exerting an inhibitory effect on ENaC-mediated sodium absorption (PubMed: 10471457). In Cystic Fibrosis (CF), defective CFTR leads to the loss of this inhibitory control, resulting in ENaC hyperactivity, excessive sodium reabsorption, and subsequent dehydration of the airway surface liquid (ASL) (PubMed: 25103157). This pathophysiological state causes the accumulation of thick, viscous mucus, leading to impaired mucociliary clearance, chronic endobronchial infections, and progressive lung damage. Pharmacological intervention targets this axis through CFTR modulators, which restore chloride transport, and ENaC inhibitors, which aim to reduce sodium hyperabsorption to rehydrate the airways and improve respiratory function (PubMed: 30639147).

Other names

ABCC7SCNN1Amiloride-sensitive sodium channelCFTR-ENaC complexSodium channel epithelial 1

CFTR potentiation (increasing channel open probability), CFTR correction (improving protein folding and trafficking), and ENaC inhibition (blocking sodium reabsorption).