Development of Epithelial Ion Transport in Fetal and Neonatal Airways

Abstract

The mode of secretion of lung liquid by the pulmonary epithelium of the sheep during late gestation and reabsorption of this liquid around the time of birth has been elucidated, but the role of different regions of the epithelium in these processes has not been examined. We studied bioelectric properties and ion flows across upper airway epithelia excised from fetal sheep and fetal and neonatal dogs. Transepithelial nasal p.d. values of human neonates were also assessed in vivo. The tracheal epithelium of fetal sheep (143 days gestation) secreted Cl^- (1.4µEq cm^-2 h^-1 hour). Na⁺ movement (1.8 µEq cm^-2 h^-1) was passive. Transepithelial p.d. (12 mV, lumen negative), short-circuit current (1.6 µEq cm^-2 h^-1) and Cl^- secretion were stimulated by isoproterenol but were not affected by amiloride. Tracheal and 4th to 6th generation bronchial epithelia of maternal sheep absorbed Na⁺; Cl^- movement was passive. Amiloride inhibited p.d., short-circuit current and Na⁺ transport, but isoproterenol had no effect. Canine fetal and neonatal (up to about 1 month) tracheas exhibited patterns of bioelectric properties, ion flow and drug response similar to those of fetal sheep trachea. Whereas the dominant ion transport deduced from drug responses of canine fetal bronchi resembled those processes of fetal and neonatal trachea, bronchi from 1 month neonates absorbed Na⁺ and responded to amiloride. Although these results suggest that Na⁺ absorption by upper airway epithelia matures after birth and proceeds from distal to proximal regions, the transepithelial p.d. values of the nasal turbinate of term and preterm infants were close to the mature value (-30 mV, lumen negative) at birth. Moreover, amiloride induced a similar inhibition of p.d. (40%) of turbinates of infants and adults. This departure from the pattern predicted from the canine studies could reflect species and/or regional differences in airway epithelial function.