Developmental regulation of lumenal lung fluid and electrolyte transport

In the fetus, there is a net secretion of liquid (LL) by the lung as a result of active transport of chloride ions. The rate of secretion and the resulting volume of LL are vital for normal lung growth but how volume is sensed and how secretion may be regulated are still unknown. Towards term under the influence of thyroid and adrenocorticoid hormones, the epithelial sodium channel (ENaC) is increasingly expressed in the pulmonary epithelium. Adrenaline released by the fetus during labour activates ENaC and produces rapid absorption of liquid in preparation for air breathing; absence of ENaC is incompatible with survival. There may be other mechanisms involved in aiding liquid clearance including changes in epithelial permeability, an effect of oxygen on both ENaC and Na/K ATPase and perhaps the influence of additional hormones on ENaC activity. Some time after birth there are further developmental changes with the appearance of other cation channels (CNG1 and perhaps NSCC) which contribute to the liquid absorptive side of the balance existing across the epithelium between secretion and absorption to produce essentially almost no net liquid movement in the postnatal lung. The evidence for these processes is discussed and areas of uncertainty indicated.