Ion transport characteristics of the murine trachea and caecum.
1. The basic defect in cystic fibrosis relates to abnormalities of ion transport in affected tissues, such as the respiratory and gastrointestinal tracts. The identification of the cystic fibrosis gene has enabled studies on the production of a cystic fibrosis transgenic mouse to be undertaken. Knowledge of normal ion transport will be necessary for the validation of any such animal model. We have therefore characterized selected responses of the murine trachea and caecum mounted in 'mini' Ussing chambers under open-circuit conditions. 2. Basal values for the trachea were: potential difference, 1.1 mV (SEM 0.2; n = 18); equivalent short-circuit current, 20.4 microA/cm2 (3.6); conductance, 18.2 mS/cm2 (1.7). Corresponding values for the caecum were: potential difference, 0.7 mV (0.1; n = 18); equivalent short-circuit current, 11.0 microA/cm2 (1.6); conductance, 14.5 mS/cm2 (1.4). 3. Amiloride (10 mumol/l) produced a significant (P less than 0.001) fall in potential difference of 43.0% (5.7) in the trachea, but had no significant effect in the caecum. 4. Subsequently, one of three protocols was used to assess the capacity of either tissue for chloride secretion. Addition of a combination of forskolin (1 mumol/l) and zardaverine (10 mumol/l) produced rises in the potential difference of 873% (509) in the trachea and 399% (202) in the caecum. Both A23187 (10 mumol/l) and phorbol dibutyrate (10 nmol/l) increased tracheal potential difference by 350% (182) and 147% (47), respectively. Neither had a significant effect in the caecum. 5. Subsequent addition of bumetanide caused a fall in the stimulated potential difference of between 39.8% and 71.7%, depending on secretagogue and tissue type.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
S N
SN
Ion Transport Laboratory, National Heart and Lung Institute, London, U.K.
Alton
E W
EW
Geddes
D M
DM
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002432:Cecum / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism; D004553:Electric Conductivity / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D002712:Chlorides; D011724:Pyridazines; D002034:Bumetanide; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D000584:Amiloride; D012964:Sodium; C066436:zardaverine