The effects of PO2 upon transepithelial ion transport in fetal rat distal lung epithelial cells.

1. Isolated rat fetal distal lung epithelial (FDLE) cells were cultured (for 48 h) at PO2 levels between 23 and 142 mmHg. Higher PO2 levels between 23 and 142 mmHg. Higher PO2 was associated with increased short circuit current (ISC) and increased abundance of the Na+ channel protein alpha-ENaC. PO2 had no effect upon ISC remaining after apical application of amiloride (10 microM). 2. Studies of cells maintained (for 48 h) at PO2 levels of 23 mmHg or 100 mmHg, and subsequently nystatin permeabilized (50 microM), showed that high PO2 increased Na+ pump capacity. This response was apparent 24 h after PO2 was raised whilst it took 48 h for the rise in ISC seen in intact cells to become fully established. Both parameters were unaffected by raising PO2 for only 30 min. 3. Basolateral application of isoprenaline (10 microM) did not affect ISC in cells maintained at 23 mmHg but evoked progressively larger responses at higher PO2. The response seen at 142 mmHg was larger than at 100 mmHg, the normal physiological alveolar PO2. 4. Isoprenaline had no effect on Na+ pump capacity at PO2 levels of 23 mmHg or 100 mmHg, but stimulated Na+ extrusion at 142 mmHg. Increasing PO2 above normal physiological levels thus allows the Na+ pump to be controlled by isoprenaline. This may explain the enhanced sensitivity to isoprenaline seen under these slightly hyperoxic conditions. 5. Changes in PO2 mimicking those occurring at birth thus exert profound influence over Na+ transport in FDLE cells and the Na+ pump could be an important locus at which this control is exercised.