Regulation of NaCl transport in the renal collecting duct: lessons from cultured cells

Abstract

The fine control of NaCl absorption regulated by hormones takes place in the distal nephron of the kidney. In collecting duct principal cells, the epithelial sodium channel (ENaC) mediates the apical entry of Na(+), which is extruded by the basolateral Na(+),K(+)-ATPase. Simian virus 40-transformed and "transimmortalized" collecting duct cell lines, derived from transgenic mice carrying a constitutive, conditionally, or tissue-specific promoter-regulated large T antigen, have been proven to be valuable tools for studying the mechanisms controlling the cell surface expression and trafficking of ENaC and Na(+),K(+)-ATPase. These cell lines have made it possible to identify sets of aldosterone- and vasopressin-stimulated proteins, and have provided new insights into the concerted mechanism of action of serum- and glucocorticoid-inducible kinase 1 (Sgk1), ubiquitin ligase Nedd4-2 (neural precursor cell-expressed, developmentally down-regulated protein 4-2), and 14-3-3 regulatory proteins in modulating ENaC-mediated Na(+) currents. Epidermal growth factor and induced leucine zipper protein have also been shown to repress and stimulate ENaC-dependent Na(+) absorption, respectively, by activating or repressing the mitogen-activated protein kinase externally regulated kinase(1/2). Overall, these findings have provided evidence suggesting that multiple pathways are involved in regulating NaCl absorption in the distal nephron.

Candidate gene variation in gilthead sea bream reveals complex spatiotemporal selection patterns between marine and lagoon habitats

“…In this case, genetic differentiation was observed among M samples and was mainly explained by the distinctiveness of the SL-M sample. This locus was associated with the ubiquitin ligase nedd4-2 (neural precursor cell-expressed, developmentally down-regulated protein 4-2) gene, a gene involved in regulation of the epithelial sodium channel in several organs, including kidney in mouse (Gormley et al 2003, Bens et al 2006. It may therefore be associated with osmoregulation in sea bream, but this function has never been investigated in fish.…”

Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells

“…In addition, we hypothesize that IL-6 might affect prostasin. We chose M-1 cells, a mammalian cell line derived from microdissected CCD of a mouse transgenic for the early region of SV40, which retains a number of the characteristics of the parental CCDs, including the expression of ENaC, high transepithelial electrical resistance (R te ), and amiloride-sensitive sodium currents (6,55). Thus, M-1 cells have been valuable tools for studying ENaC and related regulatory proteins (29,35,38,39,58,65).…”

Sodium Transport Is Modulated by p38 Kinase–Dependent Cross-Talk between ENaC and Na,K-ATPase in Collecting Duct Principal Cells

“…1 The final regulation of renal Na + reabsorption takes place in aldosterone-responsive distal tubules and collecting ducts. 2 The bulk of Na + transport in the collecting duct (CD) occurs in principal cells, where Na + enters the cell via the epithelial sodium channel (ENaC) and is extruded into the interstitial compartment via Na,K-ATPase. 3 Thus, tight control of vectorial Na + transport must be exerted on CD principal cells to achieve whole-body Na + homeostasis.…”

“…According to dietary Na + intake and aldosterone levels, CD principal cells are exposed to large physiologic variations of Na + transport. 2,3 Meanwhile, intracellular Na + concentration must be maintained within narrow ranges, which is essential for vital cellular functions, such as control of osmolality, ionic strength, and membrane potential. Therefore, apical Na + entry and basolateral Na + extrusion must be rapidly and tightly coordinated in order to match variations of Na + transport while minimizing fluctuations of intracellular Na + concentration.…”