title: Functional ENaC channels expressed in endothelial cells: a new candidate for mediating shear force.
abstract: Endothelial cells (ECs) are regulated not only by circulating hormones, but also by mechanical stresses, such as shear force. Ion channels in ECs can signal rapid changes of shear forces and are involved in controling EC permeability, proliferation, and angiogenesis. In this study, we employed patch clamping and molecular biology approaches to clarify whether the epithelial sodium channel (ENaC) is functionally expressed in ECs. The alpha-subunit of the ENaC was expressed in cultured human ECs and in intact ECs from a variety of rat arteries. In either inside- or outside-out current recordings, inward currents with a conductance of 4.83 pS were detected in cultured human ECs, where these were sensitive to micromolar amiloride. The right shift of the I-V curve in the condition of low cytoplasmic Na+ implicated that these currents were carried by Na+. The currents were mediated by ENaC channels, as confirmed by ENaC knockdown experiments. However, the activity of ENaC was nearly absent in intact ECs, because its activity was greatly inhibited by cellular molecules, partly due to 11,12-epoxyeicosatrienoic acid. In the outside-out configuration, laminar flow directly enhanced ENaC opening probability, suggesting a potential role for ENaC in mediating shear force signaling events.
authors.affiliation: Department of Physiology, The School of Medicine, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Meng
authors.forename: Sindu
authors.initials: S
authors.lastname: Mohan
authors.forename: Bipin
authors.initials: B
authors.lastname: Champaneri
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D042783:Endothelial Cells / Q000737:chemistry* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D053503:Epithelial Sodium Channels / Q000502:physiology*; D006801:Humans; D051381:Rats; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D053503:Epithelial Sodium Channels; D000584:Amiloride; D012964:Sodium