Oxygen-evoked Na+ transport in rat fetal distal lung epithelial cells

1. Monolayer cultures of rat fetal distal lung epithelial (FDLE) cells gene rated larger spontaneous short circuit currents (I-SC) when maintained (48 h) at neonatal alveolar P-O2(100 mmHg) than at fetal P-O2 (23 mmHg). When c ells were shifted between these atmospheres in order to impose a rise in P- O2 equivnlent to that seen at birth, no rise in I-SC was seen after 6 h but the response was fully established by 24 h. 2. Studies of basolaterally permeabilised cells revealed a small rise in ap ical Na+ conductance (G(Na)) 6 h after P-O2 was raised but no further chang e had occurred by 24 h. A substantial rise was, however, seen after 48 h. 3. Reporter gene assays showed that no activation of the alpha -ENaC (epith elial Naf channel alpha -subunit) promoter was discernible 24 h after P-O2 was raised but increased transcriptional activity was seen at 48 h. 4. Studies of apically permeabilised cells showed that a small rise in Napump capacity was evident 6 h after P-O2 was raised and, in common with the rise in I-SC, this effect was fully established by 24 h. The rise in I-SC thus develops 6-24 h after P-O2 is raised and is due, primarily, to increas ed Na+ pump capncity. 5. The increase in G(Na) thus coincides with activation of the alpha -ENaC promoter but these effects occur after the rise in I-SC is fully establishe d and so cannot underlie this physiological response. The increased transcr iption may he an adaptation to increased Na+ transport and not its cause.