Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1994 Jan 18;91(2):479-83.
doi: 10.1073/pnas.91.2.479.

Relationship of a non-cystic fibrosis transmembrane conductance regulator-mediated chloride conductance to organ-level disease in Cftr(-/-) mice

L L Clarke  1 , B R Grubb, J R Yankaskas, C U Cotton, A McKenzie, R C Boucher
Affiliations

Relationship of a non-cystic fibrosis transmembrane conductance regulator-mediated chloride conductance to organ-level disease in Cftr(-/-) mice

L L Clarke et al. Proc Natl Acad Sci U S A. .

Abstract

Although loss of cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl- channel function is common to all epithelia in cystic fibrosis (CF) patients, the severity of disease varies in different organs. We hypothesized that differences in disease severity in CF relate to the expression of an "alternative" plasma membrane Cl- conductance. In CF mice [Cftr(-/-); mice homozygous for Ser-489 to Xaa mutation], which do not express cAMP CFTR-mediated Cl- secretion, we surveyed organs that exhibit a range of disease severity for a Ca(2+)-mediated apical membrane epithelial Cl- conductance. This alternative conductance (Cl-a) was detected in epithelia of organs from CF mice that exhibit a mild disease phenotype (airway, pancreas) but not in epithelia with a severe phenotype (small, large intestine). We conclude that (i) there is an intracellular Ca(2+)-regulated Cl- conductance that is molecularly distinct from CFTR; and (ii) the level of expression of this alternative Cl- conductance in the epithelium is an important determinant of the severity of organ-level disease in CF.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Am J Physiol. 1990 Feb;258(2 Pt 1):C318-26 - PubMed
    1. Biochem Soc Trans. 1989 Oct;17(5):816-8 - PubMed
    1. Am J Physiol. 1991 May;260(5 Pt 1):G758-63 - PubMed
    1. Nature. 1991 Jul 4;352(6330):70-3 - PubMed
    1. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6003-7 - PubMed

Publication types

MeSH terms