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% CO(2)-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 (microA/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.
Thome
Ulrich H
UH
Department of Pediatrics, University of Alabama at Birmingham, 901 19th Street South, Birmingham, AL 35226, USA.
Davis
Ian C
IC
Nguyen
Susie Vo
SV
Shelton
Brent Jay
BJ
Matalon
Sadis
S
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D053503:Epithelial Sodium Channels; D005333:Fetus / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000196:embryology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen; D003345:Corticosterone