Epithelial Na+ channels derived from human lung are activated by shear force

During breathing the pulmonary epithelial cells are permanently exposed to physical forces and shear force (SF) in particular. In our present study we questioned whether the lung epithelial Na+ channel (hENaC) responds to shear force. For this purpose ENaC was cloned from human lung tissue, expressed in Xenopus oocytes and functionally characterized by electrophysiological techniques. Shear force in physiological relevant ranges was applied via a fluid stream. By the application of SF we obtained an increased inward current indicating an activation of hENaC. The SF-induced effect was reversible and interestingly, the response to SF was augmented by trypsin due to proteolytic cleavage. The direct activation of hENaC by SF was confirmed in outside-out single channel experiments. In five out of nine recordings an increased NPO was observed. From our observations we conclude that lung-derived hENaCs are directly activated by SF and this may represent an important feature for the regulation of pulmonary Na+ reabsorption and pulmonary fluid homeostasis. (C) 2009 Elsevier B.V. All rights reserved.