Airway surface liquid calcium modulates chloride permeability in the cystic fibrosis airway.
Patients with cystic fibrosis (CF) demonstrate a characteristic defect in epithelial chloride movement, which can be demonstrated in vivo by the nasal potential difference technique. After amiloride pretreatment, the CF airway exhibits only a transient response to perfusion with low-chloride solution, contrasting with the sustained hyperpolarization seen in control subjects. This study further investigated the response to low-chloride solution in the CF airway, examining the interaction between surface divalent ions and the low-chloride response. Sequential perfusion with amiloride, low chloride, and isoproterenol was tested in groups of subjects with CF, with the diluent containing different concentrations of calcium and magnesium, on different days. When the low-chloride response was measured with the nominally calcium-free diluents, the subjects with CF had mean (SEM) responses of 8.0 (0.7), 8.6 (2.4), and 9.6 (1.6) mV in the presence of 0, 1, and 3 mM Mg2+, respectively, significantly different from the response in the presence of divalent ions. However, the subsequent response to isoproterenol was not different in the presence or absence of divalent ions. We hypothesize that perfusion of the CF airway with nominally calcium-free solutions reduces tonic inhibition of chloride secretion.
Middleton
Peter G
PG
Cystic Fibrosis Unit, Department of Respiratory Medicine, University of Sydney, Westmead Hospital, Westmead 2145, New South Wales, Australia. peterm@westgate.wh.usyd.edu.au
Pollard
Katy A
KA
Donohoo
Elizabeth
E
Wheatley
John R
JR
Geddes
Duncan M
DM
Alton
Eric W
EW
D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling; D002413:Cations, Divalent / Q000494:pharmacology; D002712:Chlorides / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials; D010539:Permeability / Q000187:drug effects; D020545:Respiratory Mucosa / Q000378:metabolism*
D001993:Bronchodilator Agents; D002413:Cations, Divalent; D002712:Chlorides; D000584:Amiloride; D008274:Magnesium; D007545:Isoproterenol; D002118:Calcium