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% O₂ with 5% CO₂-balance N₂ and mounted in Ussing chambers for measurement of short-circuit currents (I_sc). FDLE monolayers grown in 20% O₂ 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 (μA/cm² ± SE) for 2.5-5% O₂ and 20% O₂ 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 O₂ concentration increased I_amil. FDLE cells grown at 5% O₂ expressed significantly lower levels of α-, β-, and γ-epithelial Na⁺ channel (ENaC), and of the α₁-Na⁺-K⁺-ATPase, as determined by Western blotting. We conclude that higher O₂ 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.