Modulation of aquaporin 4 and the amiloride-inhibitable sodium channel in perinatal rat lung epithelial cells.

During the perinatal period, a dramatic reversal of lung transepithelial ion and water transport occurs that involves the amiloride-inhibitable Na+ channel (ENaC). Aquaporin (AQP) water channel proteins facilitate cell membrane water transport. We now report that AQP-4, localized to basolateral membranes of airway epithelial cells, increases its mRNA expression in developing lung eightfold during the 2 days before birth to reach a peak on the first postnatal day in the lungs but not in brains or kidneys of neonatal rats. AQP-4 and the α-, β-, and γ-subunits of ENaC are both expressed by cultured rat fetal distal lung epithelial (FDLE) cells. AQP-4 and ENaC expression increase in FDLE cells cultured on uncoated permeant filters compared with matched control cells cultured on filters containing extracellular matrix derived from fetal lung epithelial cells. Similarly, AQP-4 expression increases in FDLE cells exposed to 21% O2 compared with cells exposed to 3% O2. These data demonstrate that AQP-4 expression is highest on the first day after birth in neonatal rat lungs. Exposure to ambient 21% O2 may contribute to increases in AQP-4 and ENaC expression to facilitate water transport across neonatal airway epithelia in the immediate postnatal period.