LAUSR

The many mechanisms governing NaCl absorption in the diverse parts of the renal tubule have been largely elucidated, although some of them, as neutral NaCl absorption across the cortical collecting duct or regulation through with-no-lysine (WNK) kinases have emerged only recently. Chloride channels, which are important players in these processes, at least in the distal nephron, are the focus of this review. Over the last 20-year period, experimental studies using molecular, electrophysiological, and physiological/functional approaches have deepened and renewed our views on chloride channels and their role in renal function. Two chloride channels of the ClC family, named as ClC-Ka and ClC-Kb in humans and ClC-K1 and ClC-K2 in other mammals, are preponderant and play complementary roles: ClC-K1/Ka is mainly involved in the building of the interstitial cortico-medullary concentration gradient, while ClC-K2/Kb participates in NaCl absorption in the thick ascending limb, distal convoluted tubule and the intercalated cells of the collecting duct. The two ClC-Ks might also be involved indirectly in proton secretion by type A intercalated cells. Other chloride channels in the kidneys include CFTR, TMEM16A, and probably volume-regulated LRRC8 chloride channels, whose function and molecular identity have not as yet been established. © 2019 American Physiological Society. Compr Physiol 9:301-342, 2019.