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Regulation of the epithelial $Na^{+}$ channel and airway surface liquid volume by serine proteases

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gaillard, Erol A. Kota, Pradeep Gentzsch, Martina Dokholyan, Nikolay V. Stutts, M. Jackson Tarran, Robert
Description	Country affiliation: United kingdom Author Affiliation: Gaillard EA ( Department of Infection, Immunity and Inflammation, University of Leicester, PO Box 65, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK.)
Abstract	Mammalian airways are protected from infection by a thin film of airway surface liquid (ASL) which covers airway epithelial surfaces and acts as a lubricant to keep mucus from adhering to the epithelial surface. Precise regulation of ASL volume is essential for efficient mucus clearance and too great a reduction in ASL volume causes mucus dehydration and mucus stasis which contributes to chronic airway infection. The epithelial Na(+) channel (ENaC) is the rate-limiting step that governs Na(+) absorption in the airways. Recent in vitro and in vivo data have demonstrated that ENaC is a critical determinant of ASL volume and hence mucus clearance. ENaC must be cleaved by either intracellular furin-type proteases or extracellular serine proteases to be active and conduct Na(+), and this process can be inhibited by protease inhibitors. ENaC can be regulated by multiple pathways, and once proteolytically cleaved ENaC may then be inhibited by intracellular second messengers such as cAMP and PIP(2). In the airways, however, regulation of ENaC by proteases seems to be the predominant mode of regulation since knockdown of either endogenous serine proteases such as prostasin, or inhibitors of ENaC proteolysis such as SPLUNC1, has large effects on ENaC activity in airway epithelia. In this review, we shall discuss how ENaC is proteolytically cleaved, how this process can regulate ASL volume, and how its failure to operate correctly may contribute to chronic airway disease.
File Format	HTM / HTML
ISSN	00316768
e-ISSN	14322013
DOI	10.1007/s00424-010-0827-z
Journal	Pflügers Archiv - European Journal of Physiology
Issue Number	1
Volume Number	460
Language	English
Publisher	Springer
Publisher Date	2010-06-01
Publisher Place	Germany
Access Restriction	Open
Subject Keyword	Discipline Physiology Epithelial Sodium Channels Metabolism Ion Channel Gating Mucociliary Clearance Respiratory Mucosa Enzymology Respiratory System Serine Proteases Animals Chemistry Protein Conformation Respiratory Tract Diseases Second Messenger Systems Serine Proteinase Inhibitors Structure-activity Relationship Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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