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Am J Physiol Lung Cell Mol Physiol (December 14, 2001). doi:10.1152/ajplung.00355.2001
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Articles in PresS, published online ahead of print December 14, 2001
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00355.2001
Submitted on September 4, 2001
Accepted on December 3, 2001

Hypoxia decreases active Na transport across primary rat alveolar epithelial cell monolayers

Heimo Mairbaeurl1*, Katrin Mayer1, Kwang-Jin Kim2, Zea Borok2, Peter Baertsch1, and Edward D Crandall2

1 Department of Internal Medicine VII, University of Heidelberg, Heidelberg, Germany
2 Department of Medicine, University of Southern California, Los Angeles, CA, USA

* To whom correspondence should be addressed. E-mail: kjkim{at}hsc.usc.edu.

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 about 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 hours, 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.




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