Chloride secretion by renal collecting ducts.

Abstract

Renal collecting ducts maintain NaCl homeostasis by fine-tuning urinary excretion to balance dietary salt intake. This review focuses on recent studies on transcellular Cl secretion by collecting ducts, its regulation and its role in cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Lumens of nonperfused rat medullary collecting ducts collapse in control media but expand with fluid following treatment with cAMP, demonstrating the capacity for both salt absorption and secretion. Recently, inhibition of apical epithelial Na channels (ENaC) unmasked Cl secretion in perfused mouse cortical collecting ducts (CCDs), involving Cl uptake by basolateral NKCC1 and efflux through apical Cl channels. AVP, the key hormone for osmoregulation, promotes cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl secretion. In addition, prostaglandin E2 stimulates Cl secretion through both CFTR and Ca-activated Cl channels. Renal Cl secretion has been commonly overlooked because of the overwhelming capacity for the nephron to reabsorb NaCl from the glomerular filtrate. In ADPKD, Cl secretion plays a central role in the accumulation of cyst fluid and the remarkable size of the cystic kidneys. Investigation of renal Cl secretion may provide a better understanding of NaCl homeostasis and identify new approaches to reduce cyst growth in PKD.