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 r esults in respiratory distress. To investigate potential mechanisms, the on togeny and cellular distribution of the alpha ENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lun gs using nonradioisotopic in situ hybridization. Surprisingly, alpha ENaC e xpression was detected at the embryonic stage of normal lung development (4 to 5 wk gestation) when expression was localized to the fetal lung bud epi thelium. By late gestation, ENaC was expressed in the conductive and respir atory airway epithelium, serous cells, and the distal lung unit in an alveo lar type II (ATII) epitheliumlike distribution. Significant alpha ENaC expr ession was found in newborn lung diseases associated with respiratory distr ess. One explanation is that alpha ENaC mRNA is constitutively expressed, a nd that activity Is regulated, at least in part, at the post-transcriptiona l level. Alternative explanations are that the expression of the beta or ga mma ENaC subunits may be impaired in certain newborn lung diseases or that alternate Na+ permeant channels or transporters are important to lung liqui d absorption in humans at birth.