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Published ahead of print on August 27, 2008
J Am Soc Nephrol 19: 1845-1854, 2008
© 2008 American Society of Nephrology
doi: 10.1681/ASN.2008020225

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Brief Review

Mechanisms of ENaC Regulation and Clinical Implications

Vivek Bhalla* and Kenneth R. Hallows{dagger}

* Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California; and {dagger} Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Correspondence: Dr. Kenneth R. Hallows, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, S976.1 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261. Phone: 412-648-9580; Fax: 412-383-8956; E-mail: hallows{at}pitt.edu

The epithelial Na+ channel (ENaC) transports Na+ across tight epithelia, including the distal nephron. Different paradigms of ENaC regulation include extrinsic and intrinsic factors that affect the expression, single-channel properties, and intracellular trafficking of the channel. In particular, recent discoveries highlight new findings regarding proteolytic processing, ubiquitination, and recycling of the channel. Understanding the regulation of this channel is critical to the understanding of various clinical phenomena, including normal physiology and several diseases of kidney and lung epithelia, such as blood pressure (BP) control, edema, and airway fluid clearance. Significant progress has been achieved in this active field of research. Although ENaC is classically thought to be a mediator of BP and volume status through Na+ reabsorption in the distal nephron, several studies in animal models highlight important roles for ENaC in lung pathophysiology, including in cystic fibrosis. The purpose of this review is to highlight the various modes and mechanisms of ENaC regulation, with a focus on more recent studies and their clinical implications.




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R. S. Edinger, J. Lebowitz, H. Li, R. Alzamora, H. Wang, J. P. Johnson, and K. R. Hallows
Functional Regulation of the Epithelial Na+ Channel by I{kappa}B Kinase-{beta} Occurs via Phosphorylation of the Ubiquitin Ligase Nedd4-2
J. Biol. Chem., January 2, 2009; 284(1): 150 - 157.
[Abstract] [Full Text] [PDF]




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