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Control of Epithelial Ion Transport by Cl- and PDZ Proteins

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Journal J Membr Biol
Date 2004 Sep 24
PMID 15383919
Citations 5
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Abstract

Inhibition of epithelial Na+ channels (ENaC) by the cystic fibrosis transmembrane conductance regulator (CFTR) has been demonstrated previously. Recent studies suggested a role of cytosolic Cl- for the interaction of CFTR with ENaC, when studied in Xenopus oocytes. In the present study we demonstrate that the Na+ / H+ -exchanger regulator factor (NHERF) controls expression of CFTR in mouse collecting duct cells. Inhibition of NHERF largely attenuates CFTR expression, which is paralleled by enhanced Ca(2+) -dependent Cl- secretion and augmented Na+ absorption by the ENaC. It is further demonstrated that epithelial Na+ absorption and ENaC are inhibited by cytosolic Cl- and that stimulation by secretagogues enhances the intracellular Cl- concentration. Thus, the data provide a clue to the question, how epithelial cells can operate as both absorptive and secretory units: Increase in intracellular Cl- during activation of secretion will inhibit ENaC and switch epithelial transport from salt absorption to Cl- secretion.

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