Modulation of sodium transport in fetal alveolar epithelial cells by oxygen and corticosterone

Regulation of active Na+ transport across fetal distal lung epithelial cells (FDLE) by corticosterone (CST), corticotropin-releasing hormone (CRH), and oxygen tension may be crucial for postnatal adaptation. FDLE isolated from 19-day rat fetuses (term: 22 days) were grown on permeable supports to confluent monolayers (duration 3 days) in 2.5, 5, 12, or 20% O-2 with 5% CO2-balance N-2 and mounted in Ussing chambers for measurement of short-circuit currents (I-sc). FDLE monolayers grown in 20% O-2 had significantly higher levels of total I-sc and of their amiloride-sensitive (I-amil) and ouabain-sensitive (I-ouab) components than hypoxic cells. Values (muA/cm(2) +/- SE) for 2.5-5% O-2 and 20% O-2 were, respectively, I-sc 5.3 +/- 0.2 vs. 8.4 +/- 0.3 (P < 0.001), I-amil 3.4 +/- 0.2 vs. 4.3 +/- 0.2 (P < 0.01), and I-ouab 3.4 +/- 0.6 vs. 9.1 +/- 0.6 (P < 0.001). Addition of CST but not CRH to the culture medium at any O-2 concentration increased I-amil. FDLE cells grown at 5% O-2 expressed significantly lower levels of alpha-, beta-, and gamma-epithelial Na+ channel (ENaC), and of the alpha(1)-Na+-K+-ATPase, as determined by Western blotting. We conclude that higher O-2 concentrations increased total vectorial Na+ transport, and the function of Na+-K+-ATPase and apical amiloride-sensitive Na+ conductance, whereas CST only increased ENaC function.