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New insights regarding epithelial Na+ channel regulation and its role in the kidney, immune system and vasculature

Mutchler, Stephanie M.a,b; Kleyman, Thomas R.a,b,c

Current Opinion in Nephrology and Hypertension: March 2019 - Volume 28 - Issue 2 - p 113–119
doi: 10.1097/MNH.0000000000000479

Purpose of review This review describes recent findings regarding the epithelial Na+ channel (ENaC) and its roles in physiologic and pathophysiologic states. We discuss new insights regarding ENaC's structure, its regulation by various factors, its potential role in hypertension and nephrotic syndrome, and its roles in the immune system and vasculature.

Recent findings A recently resolved structure of ENaC provides clues regarding mechanisms of ENaC activation by proteases. The use of amiloride in nephrotic syndrome, and associated complications are discussed. ENaC is expressed in dendritic cells and contributes to immune system activation and increases in blood pressure in response to NaCl. ENaC is expressed in endothelial ENaC and has a role in regulating vascular tone.

Summary New findings have emerged regarding ENaC and its role in the kidney, immune system, and vasculature.

aDepartment of Medicine

bDepartment of Pharmacology and Chemical Biology

cDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Correspondence to Thomas R. Kleyman, MD, Renal-Electrolyte Division, A919 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA. E-mail:

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.