The Epithelial Na+ Channel: Cell Surface Insertion and Retrieval in Na+ Homeostasis and Hypertension
Peter M. Snyder
Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52422
Correspondence: Address all correspondence and requests for reprints to: Peter M. Snyder, M.D., Department of Internal Medicine, University of Iowa College of Medicine, 371 EMRB, Iowa City, Iowa 52242. E-mail: psnyder{at}blue.weeg.uiowa.edu
The epithelial Na+ channel (ENaC) forms the pathway for Na+absorption in the kidney collecting duct and other epithelia.Dominant gain-of-function mutations cause Liddle’s syndrome,an inherited form of hypertension resulting from excessive renalNa+ absorption. Conversely, loss-of-function mutations causepseudohypoaldosteronism type I, a disorder of salt wasting andhypotension. Thus, ENaC has a critical role in the maintenanceof Na+ homeostasis and blood pressure control. Altered Na+ absorptionin the lung may also contribute to the pathogenesis of cysticfibrosis. Epithelial Na+ absorption is regulated in large partby mechanisms that control the expression of ENaC at the cellsurface. Nedd4, a ubiquitin protein ligase, binds to ENaC andtargets the channel for endocytosis and degradation. Liddle’ssyndrome mutations disrupt the interaction between ENaC andNedd4, resulting in an increase in the number of ENaC channelsat the cell surface. Aldosterone and vasopressin also regulateNa+ absorption to defend against hypotension and hypovolemia.Both hormones increase the expression of ENaC at the cell surface.The goal of this review is to summarize recent data on the regulationof ENaC expression at the cell surface.
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