title: Hypoxia decreases active Na transport across primary rat alveolar epithelial cell monolayers.
abstract: Hypoxia has been reported to inhibit activity and expression of ion transporters of alveolar epithelial cells. This study extended those observations by investigating the mechanisms underlying inhibition of active Na transport across primary cultured adult rat alveolar epithelial cell monolayers grown on polycarbonate filters. Cell monolayers were exposed to normoxia and hypoxia (1.5% and 5% O(2), 5% CO(2)), and resultant changes in bioelectric properties [i.e., short-circuit current (I(sc)) and transepithelial resistance (R(t))] were measured in Ussing chambers. Results showed that I(sc) decreased with duration of exposure to hypoxia, while relatively little change was observed for R(t). In normoxia, amiloride inhibited approximately 70% of I(sc). The amiloride-sensitive portion of I(sc) decreased over time of exposure to hypoxia, whereas the magnitude of the amiloride-insensitive portion of I(sc) was not affected. Na pump capacity measured after permeabilization of the apical plasma membrane with amphotericin B decreased in monolayers exposed to 1.5% O(2) for 24 h, as did the capacity of amiloride-sensitive Na uptake measured after imposing an apical to basolateral Na gradient and permeabilization of the basolateral membrane. These results demonstrate that exposure to hypoxia inhibits alveolar epithelial Na reabsorption by reducing the rates of both apical amiloride-sensitive Na entry and basolateral Na extrusion.
authors.affiliation: Medical Clinic and Polyclinic, Department of Internal Medicine VII, Sports Medicine, University of Heidelberg, Hospitalstrasse 3, Geb. 4100, 69115 Heidelberg, Germany. heimo_mairbaurl@med.uni-heidelberg.de
authors.forename: Heimo
authors.initials: H
authors.lastname: Mairbäurl
authors.forename: Katrin
authors.initials: K
authors.lastname: Mayer
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Zea
authors.initials: Z
authors.lastname: Borok
authors.forename: Peter
authors.initials: P
authors.lastname: Bärtsch
authors.forename: Edward D
authors.initials: ED
authors.lastname: Crandall
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D004232:Diuretics / Q000494:pharmacology; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015633:Extravascular Lung Water / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004232:Diuretics; D015222:Sodium Channels; D000584:Amiloride; D000666:Amphotericin B; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase