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Control of Epithelial Ion Transport by Cl− and PDZ Proteins

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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 Ca2+-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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Abbreviations

cAMP:

cyclic adenosine monophosphate

CFTR:

cystic fibrosis transmembrane conductance regulator

ENaC:

epithelial Na+ channel

IBMX:

3-isobutyl-1-methylxanthine

NHERF1:

Na+/H+-exchanger regulator factor

TKA-1:

tyrosine kinase activating protein

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Acknowledgments

This work was supported by NHMRC 252823 and ARC A00104609, the Else Kröner-Fresenius Stiftung. The excellent technical assistance by Ms. Ernestine Tartler and Ms. Agnes Paech is gratefully acknowledged. We thank Prof. Alan Verkman and Dr. Ma for providing us with the YFP constructs and Prof E. Weinman for supplying the NHERF antibody.

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Authors and Affiliations

  1. Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053, Regensburg, Germany

    R. Schreiber, A. Boucherot, B. Mürle & K. Kunzelmann

  2. Department of Physiology and Pharmacology, University of Queensland, QLD, Australia

    J. Sun

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  1. R. Schreiber
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  2. A. Boucherot
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Correspondence to K. Kunzelmann.

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Schreiber, R., Boucherot, A., Mürle, B. et al. Control of Epithelial Ion Transport by Cl− and PDZ Proteins. J Membrane Biol 199, 85–98 (2004). https://doi.org/10.1007/s00232-004-0679-6

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