Premium
Role of sodium pump β1 subunit in adult mouse lung alveolar fluid homeostasis
Author(s) -
Flodby Per,
Borok Zea,
Gao Danping,
Kim Yong Ho,
Kim Kwang-Jin,
Crandall Edward D
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1069.6
Subject(s) - lung , epithelial sodium channel , homeostasis , chemistry , endocrinology , protein subunit , alveolar epithelium , medicine , knockout mouse , sodium , microbiology and biotechnology , biology , receptor , biochemistry , gene , organic chemistry
Regulation of salt and water balance in the lung involves active alveolar epithelial ion (Na + ) transport. The basolateral Na + , K + ‐ ATPase (sodium pump) plays a crucial role by creating ionic and osmotic gradients across alveolar epithelium, leading to absorption of salt and water from alveolar spaces. The sodium pump contains three subunits (α,β,γ). The β1 subunit is the most highly expressed β isoform in adult lung, being present in both alveolar epithelial type I (AT1) and type II (AT2) cells. To elucidate the importance of the β1 subunit in adult mouse lung and its relative importance in AT1 vs AT2 cell function, we generated mice with knockout of the β1 subunit gene ( Atp1b1 ) specifically in AT1 cells ( Atp1b1 Aqp5‐cre mice) or in both AT1 and AT2 cells ( Atp1b1 Sftpc‐cre mice). Lung transport function was assessed by alveolar fluid clearance (AFC) measurements in anesthetized mice. AFC in Atp1b1 Aqp5‐cre mice was reduced 45%, while AFC in Atp1b1 Sftpc‐cre mice was reduced almost 80%, compared to floxed controls ( Atp1b1 F/F ). Terbutaline, a β‐adrenergic agonist, increased AFC in Atp1b1 Sftpc‐cre mice (from 6.6 to 30.8% per hour) compared to controls (from 29.8 to 36.4% per hour). These data (1) indicate significant contributions to AFC from both AT1 and AT2 cells and (2) suggest the presence of β‐agonist‐inducible mechanisms that compensate for lack of the β1 subunit. Funding: NIH; Hastings and Whittier Foundations