title: Hyperabsorption of Na+ and raised Ca(2+)-mediated Cl- secretion in nasal epithelia of CF mice.
abstract: We investigated the effect of homozygous genetic disruption of the murine cystic fibrosis transmembrane regulator (CFTR) gene on regulation of the rates of Na+ absorption and Cl- secretion by nasal epithelia in cystic fibrosis (CF) mice. The basal in vivo nasal potential difference (PD; -28.8 +/- 1.8 mV, n = 10) and amiloride-sensitive PD (delta 13.8 +/- 1.0 mV, n = 10) were raised in CF mice compared with controls [-7.8 +/- 0.8 mV, n = 14 (basal); delta 4.5 +/- 0.7 mV, n = 14 (amiloride)], consistent with raised Na+ transport. In vitro studies of freshly excised nasal epithelia confirmed that CF epithelia exhibited a greater basal equivalent short-circuit current (Ieq; 63.5 +/- 12 microA/cm2, n = 15) vs. control (30.2 +/- 7.2 microA/cm2, n = 16) and amiloride-sensitive Ieq (delta 46.2 +/- 12.5 microA/cm2) vs. control (delta 11.3 +/- 4.5 microA/cm2). Tissue from normal mice failed to secrete Cl- in response to ionomycin (delta Ieq: -1.2 +/- 1.9 microA/cm2, n = 18), whereas CF murine tissue responded with a large rise in Ieq (delta 55.1 +/- 19.1 microA/cm2, n = 13). We conclude that CF murine nasal epithelia exhibit Na+ hyperabsorption, providing strong evidence for a regulatory link between CFTR and Na+ channel activity in airway epithelia. We speculate that upregulation of the Ca(2+)-mediated Cl- secretory pathway buffers the severity of airway disease in the CF mouse.
authors.affiliation: Division of Pulmonary Diseases, University of North Carolina at Chapel Hill 27599.
authors.forename: B R
authors.initials: BR
authors.lastname: Grubb
authors.forename: R N
authors.initials: RN
authors.lastname: Vick
authors.forename: R C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000235:genetics* / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D006720:Homozygote; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009297:Nasal Mucosa / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D002034:Bumetanide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D015759:Ionomycin; D000584:Amiloride; D012964:Sodium; D002118:Calcium