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.(ABSTRACT TRUNCATED AT 250 WORDS)
Barker
P M
PM
Department of Pediatrics, University of North Carolina at Chapel Hill 27599-7220, USA.
Brigman
K K
KK
Paradiso
A M
AM
Boucher
R C
RC
Gatzy
J T
JT
D000818:Animals; D002118:Calcium / Q000502:physiology; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004594:Electrophysiology; D005260:Female; D006579:Heterozygote; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D014132:Trachea / Q000196:embryology / Q000503:physiopathology*
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002118:Calcium