RESEARCH ARTICLE


The Epithelial Sodium Channel ENaC and its Regulators in the Epidermal Permeability Barrier Function



Simona Frateschi1, Roch-Philippe Charles1, #, Edith Hummler*, 1
1 1Département de Pharmacologie et de Toxicologie, University of Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland


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Creative Commons License
© 2010 Frateschi et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Département de Pharmacologie et de Toxicologie, Université de Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Swizerland; Tel: +41-216925357; Fax: +41- 216925355; E-mail: Edith.Hummler@unil.ch #
§ Present Address: UCSF Cancer Research Institute, San Francisco, CA, USA


Abstract

The highly amiloride-sensitive epithelial sodium channel ENaC is well known to be involved in controlling whole body sodium homeostasis and lung liquid clearance. ENaC expression has also been detected in the skin of amphibians and mammals. Mice lacking ENaC expression lose rapidly weight associated with an epidermal barrier defect that develops following birth. This dehydration is accompanied with a highly abnormal lipid matrix composition and an impaired skin surface acidification. This strongly suggests a role of ENaC in the maturation of barrier function rather than in the prenatal generation of the barrier, and may be as such an important modulator for skin hydration. In parallel, gene targeting experiments of regulators of ENaC activity, membrane serine proteases, also termed channel activating proteases, like CAP1/Prss8 and matriptase/MT-SP1 by themselves have been shown to be crucial for the epidermal barrier function. In our review, we mainly focus on the role of ENaC and its regulators in the skin and discuss their importance in the epidermal permeability barrier function.

Keywords: Sodium channel, transmembrane ion flux, regulators or ENaC, serine protease, barrier dysfunction.