Hormonal and Nonhormonal Mechanisms of Regulation of the Na,K-Pump in Collecting Duct Principal Cells

In the kidney, the collecting duct (CD) is the site of final Na+ reabsorption, according to Na+ balance requirements. In this segment of the renal tubule, principal cells may reabsorb up to 5% of the filtered sodium. The driving force for this process is provided by the basolateral Na,K-adenosine triphosphatase (ATPase) (sodium pump). Na,K-ATPase activity and expression in the CD are modulated physiologically by hormones (aldosterone, vasopressin, and insulin) and nonhormonal factors including intracellular [Na+] and extracellular osmolality. In this article, we review the short- and long-term hormonal regulation of Na,K-ATPase in CD principal cells, and we analyze the integrated network of implicated signaling pathways with an emphasis on the latest findings.