Selected contribution: limiting Na(+) transport rate in airway epithelia from alpha-ENaC transgenic mice: a model for pulmonary edema.
The amiloride-sensitive epithelial Na(+) channel (ENaC) is essential for fluid clearance from the airways. An experimental animal model with a reduced expression of ENaC, the alpha-ENaC transgenic rescue mouse, is prone to develop edema under hypoxia exposure. This strongly suggests an involvement of ENaC in the pathogenesis of pulmonary edema. To investigate the pathogenesis of this type of edema, primary cultures of tracheal cells from these mice were studied in vitro. An ~60% reduction in baseline amiloride-sensitive Na(+) transport was observed, but the pharmacological characteristics and physiological regulation of the channel were similar to those observed in cells from wild-type mice. Aprotinin, an inhibitor of serine proteases, blocked 50-60% of the basal transepithelial current, hypoxia induced downregulation of Na(+) transport, and beta-adrenergic stimulation was effective to stimulate Na(+) transport after the hypoxia-induced decrease. When downregulation of ENaC activity (such as observed under hypoxia) is added to a low "constitutive" ENaC expression, the resulting reduced Na(+) transport rate may be insufficient for airway fluid clearance and favor pulmonary edema.
Olivier
Reynald
R
Institut de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland.
Scherrer
Urs
U
Horisberger
Jean-Daniel
JD
Rossier
Bernard C
BC
Hummler
Edith
E
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D053503:Epithelial Sodium Channels; D000860:Hypoxia / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D011654:Pulmonary Edema / Q000378:metabolism*; D012016:Reference Values; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
D053503:Epithelial Sodium Channels; D015842:Serine Proteinase Inhibitors; D015222:Sodium Channels; D000584:Amiloride; D007611:Aprotinin; D012964:Sodium; D013726:Terbutaline