Cl- secretion by trachea of CFTR (+/-) and (-/-) fetal mouse.

The absence of pathologic changes in newborn cystic fibrosis (CF) lung suggests that the fetal CF lung is inflated with a normal volume of liquid and that Cl- is secreted through paths other than the cystic fibrosis transmembrane conductance regulator (CFTR)-associated Cl- channel. We studied liquid content of distal lung and transepithelial electrical potential difference (PD) of cultured cystic tracheal explants from 16 to 19 day gestation fetal mice of CFTR (+/-)(heterozygous) females that were mated with CFTR (-/-) "knockout" males. Distal lung water content was not affected by fetal genotype. Basal PDs were not different (CFTR (+/-), 8.6 mV, and CFTR (-/-), 9.1 mV), and PDs of both groups were inhibited by intraluminal injection of amiloride (10(-4) M) (-25%) and after addition of bumetanide (10(-4) M) to the bath (-40%). Terbutaline (3 x 10(-5) M) induced a similar increase in PD (about 65%) in both groups. Intraluminal injection of ionomycin (2 x 10(-5) and 5 x 10(-6) M) raised PD in both groups (CFTR (+/-) by 32 and 27% and CFTR (-/-) by 41 and 11%). All of the increase in PD induced by terbutaline and ionomycin was inhibited by bumetanide. The PD response to terbutaline was not attenuated by pretreatment with ionomycin or the Ca2+ chelator BAPTA (10(-4) M). Ionomycin or ATP, but not terbutaline, increased intracellular Ca2+ concentration of isolated cultured tracheal epithelial cells

Potential Difference across Respiratory Epithelia in Cystic Fibrosis

To the Editor: In their paper describing increased electric potential difference across respiratory epithelia in cystic fibrosis (December 17 issue1) Knowles et al. mentioned that the time course of indomethacin's action on the bioelectric properties of respiratory epithelia was not well documented. This is not correct; we have previously reported details of indomethacin's effect on electrical properties and on transport of sodium and chloride across canine tracheal mucosa in vitro

Electrical Properties of Tracheal Epithelium in Cystic Fibrosis

To the Editor: As reported by Knowles et al. in the issue of December 17, 1981, in vivo measurements of potential difference across the trachea in patients with cystic fibrosis were significantly greater than in control subjects. (P<0.05).* Superfusion of the luminal surface of the trachea with amiloride (10-4 M) reduced the potential difference by 85 per cent in patients, as compared with 25 per cent in controls, suggesting that the increased potential difference in cystic fibrosis is due to an increase in amiloride-sensitive sodium absorption