Browse by author
Lookup NU author(s): Dr James Garnett,
Dr Michael Gray
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
In most HCO3--secreting epithelial tissues, SLC26 Cl-/HCO3- transporters work in concert with the cystic fibrosis transmembrane conductance regulator (CFTR) to regulate the magnitude and composition of the secreted fluid, a process that is vital for normal tissue function. By contrast, CFTR is regarded as the only exit pathway for HCO3- in the airways. Here we show that Cl-/HCO3- anion exchange makes a major contribution to transcellular HCO3- transport in airway serous cells. Real-time measurement of intracellular pH from polarized cultures of human Calu-3 cells demonstrated cAMP/PKA-activated Cl--dependent HCO3- transport across the luminal membrane via CFTR-dependent coupled Cl-/HCO3- anion exchange. The pharmacological and functional profile of the luminal anion exchanger was consistent with SLC26A4 (pendrin), which was shown to be expressed by quantitative RT-PCR, Western blot, and immunofluorescence. Pendrin-mediated anion exchange activity was confirmed by shRNA pendrin knockdown (KD), which markedly reduced cAMP-activated Cl-/HCO3- exchange. To establish the relative roles of CFTR and pendrin in net HCO3- secretion, transepithelial liquid secretion rate and liquid pH were measured in wild type, pendrin KD, and CFTR KD cells. cAMP/PKA increased the rate and pH of the secreted fluid. Inhibiting CFTR reduced the rate of liquid secretion but not the pH, whereas decreasing pendrin activity lowered pH with little effect on volume. These results establish that CFTR predominately controls the rate of liquid secretion, whereas pendrin regulates the composition of the secreted fluid and identifies a critical role for this anion exchanger in transcellular HCO3- secretion in airway serous cells.
Author(s): Garnett JP, Hickman E, Burrows R, Hegyi P, Tiszlavicz L, Cuthbert AW, Fong PY, Gray MA
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Print publication date: 01/11/2011
ISSN (print): 0021-9258
ISSN (electronic): 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology, Inc.
Altmetrics provided by Altmetric