Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in thekidney: Hormonal control

Tubular reabsorption of filtered sodium is quantitatively the main contribu tion of kidneys to salt and water homeostasis. The transcellular reabsorpti on of sodium proceeds by a two-step mechanism: Na+-K+-ATPase-energized baso lateral active extrusion of sodium permits passive apical entry through var ious sodium transport systems. In the past 15 years, most of the renal sodi um transport systems (Na+-K+-ATPase, channels, cotransporters, and exchange rs) have been characterized at a molecular level. Coupled to the methods de veloped during the 1965-1985 decades to circumvent kidney heterogeneity and analyze sodium transport at the level of single nephron segments, cloning of the transporters allowed us to move our understanding of hormone regulat ion of sodium transport from a cellular to a molecular level. The main purp ose of this review is to analyze how molecular events at the transporter le vel account for the physiological changes in tubular handling of sodium pro moted by hormones. In recent years, it also became obvious that intracellul ar signaling pathways interacted with each other, leading to synergisms or antagonisms. A second aim of this review is therefore to analyze the integr ated network of signaling pathways under-lying hormone action. Given the ce ntral role of Na+-K+-ATPase in sodium reabsorption, the first part of this review focuses on its structural and functional properties, with a special mention of the specificity of Na+-K+-ATPase expressed in renal tubule. in a second part, the general mechanisms of hormone signaling are briefly intro duced before a more detailed discussion of the nephron segment-specific exp ression of hormone receptors and signaling pathways. The three following pa rts integrate the molecular and physiological aspects of the hormonal regul ation of sodium transport processes in three nephron segments: the proximal tubule, the thick ascending limb of Henle's loop, and the collecting duct.