Epithelial Na(+) channel (ENaC) expression in the developing normal and abnormal human perinatal lung.

Impaired lung epithelial Na+ channel (ENaC) activity at the time of birth results in respiratory distress. To investigate potential mechanisms, the ontogeny and cellular distribution of the alpha ENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lungs using nonradioisotopic in situ hybridization. Surprisingly, alpha ENaC expression was detected at the embryonic stage of normal lung development (4 to 5 wk gestation) when expression was localized to the fetal lung bud epithelium. By late gestation, ENaC was expressed in the conductive and respiratory airway epithelium, serous cells, and the distal lung unit in an alveolar type II (ATII) epitheliumlike distribution. Significant alpha ENaC expression was found in newborn lung diseases associated with respiratory distress. One explanation is that alpha ENaC mRNA is constitutively expressed, and that activity Is regulated, at least in part, at the post-transcriptional level. Alternative explanations are that the expression of the beta or gamma ENaC subunits may be impaired in certain newborn lung diseases or that alternate Na+ permeant channels or transporters are important to lung liquid absorption in humans at birth.