Epithelial chloride secretion

Epithelial chloride secretion is a critical physiological process that regulates the movement of salt and water across epithelial surfaces in organs such as the lungs, intestines, and exocrine glands [1, 12]. This transepithelial transport is achieved through the coordinated action of several proteins, primarily the apical Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and calcium-activated chloride channels (CaCCs) like TMEM16A, supported by basolateral entry via the Sodium-Potassium-Chloride Cotransporter 1 (NKCC1) [6, 11]. The efflux of chloride ions into the lumen generates an osmotic driving force for the movement of water and sodium, which is essential for maintaining the hydration and fluidity of mucosal layers [12, 14]. Clinical manifestations of disrupted chloride secretion include cystic fibrosis, where deficient transport leads to thick, obstructive mucus, and secretory diarrhea, where excessive transport caused by bacterial or viral toxins results in massive fluid loss [1, 11, 14]. Pharmacological agents target this process by either stimulating secretion (e.g., ivacaftor for cystic fibrosis) or inhibiting it (e.g., crofelemer for diarrhea) to restore homeostatic fluid balance [2, 6].

Other names

Epithelial anion secretionTransepithelial chloride transportIntestinal chloride secretionAirway chloride secretion

Pharmacological modulation of epithelial chloride secretion involves the activation of apical chloride channels (e.g., CFTR potentiators), the correction of protein folding and trafficking (e.g., CFTR correctors), the inhibition of apical anion efflux (e.g., CaCC or CFTR inhibitors for diarrhea), or the activation of alternative secretory pathways such as ClC-2 to bypass defective components [2, 4, 6, 11].