Alveolar Epithelial Ion and Fluid Transport Hypoxia decreases active Na transport across primary rat alveolar epithelial cell monolayers

Mairbäurl, Heimo, Katrin Mayer, Kwang-Jin Kim, Zea Borok, Peter Bärtsch, and Edward D. Crandall. Hypoxia decreases active Na transport across primary rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 282: L659–L665, 2002. First published December 14, 2001; 10.1152/ajplung.00355.2001.—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% O2, 5% CO2), and resultant changes in bioelectric properties [i.e., short-circuit current (Isc) and transepithelial resistance (Rt)] were measured in Ussing chambers. Results showed that Isc decreased with duration of exposure to hypoxia, while relatively little change was observed for Rt. In normoxia, amiloride inhibited 70% of Isc. The amiloride-sensitive portion of Isc decreased over time of exposure to hypoxia, whereas the magnitude of the amiloride-insensitive portion of Isc was not affected. Na pump capacity measured after permeabilization of the apical plasma membrane with amphotericin B decreased in monolayers exposed to 1.5% O2 for 24 h, as did the capacity of amiloridesensitive 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.