Influence of gestational age on potential difference across fetal type II alveolar epithelium in alveolar-like structures

The active transport of ions across fetal pulmonary epithelium results in lung fluid secretion. This study investigated the potential difference (PD) across fetal type II alveolar epithelium, one of the several epithelial cell types in the fetal lung. Aggregates of these cells in alveolar-like structures (ALS) underwent microelectrode impalement to determine the effect of gestational age, and drugs on transcellular PD. In 6 ALS, the intraluminal position of the electrode was confirmed by fluorescent imaging after iontophoretic injection of Lucifer Yellow VS dye. The average PD recorded from the lumens of ALS harvested from 20-day fetal rats was 11.8 +/- (SE) 0.48 mV (lumen-negative; n = 164). Exposure to ouabain 10(-3) M significantly reduced PD from control values of 12.3 +/- (SE) 0.87 to 8.1 +/- (SE) 0.95 mV (p less than 0.01, n = 107) in ALS obtained from 20-day fetal rats. Terbutaline 10(-3) M and furosemide 10(-3) M did not influence PD. Cells obtained from fetuses near term showed a significant reduction in PD. ALS from 18-day (n = 53), 20-day (n = 164) and 22-day (n = 56) fetuses measured 13.5 +/- 0.62, 11.8 +/- 0.48 and 9.3 +/- 0.49 mV, respectively (p less than 0.05 day 18 vs. day 22). These results demonstrate that fetal type II cells grown in organotypic culture maintain a larger transcellular electrical gradient than previously reported. PD decreases with increasing gestational age and can be reduced by the Na-K ATPase inhibitor ouabain.