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Effect of Cytosolic pH on Epithelial Na+ Channel in Normal and Cystic Fibrosis Sweat Ducts

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Abstract

The activities of cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel and the amiloride-sensitive epithelial Na+ channel (ENaC) are acutely coordinated in the sweat duct. However, the mechanisms responsible for cross-talk between these ion channels are unknown. Previous studies indicated that luminal pH of sweat ducts varies over 3 pH units and that the cytoplasmic pH affects both CFTR and ENaC. Therefore, using basolaterally α-toxin-permeabilized apical membrane preparations of sweat ducts as an experimental system, we tested the hypothesis that the cytosolic pH may mediate the cross-talk between CFTR and ENaC. We showed that while luminal pH had no effect, cytosolic pH acutely affected ENaC activity. That is, acidic pH inhibited, while basic pH activated, ENaC. pH regulation of ENaC appears to be independent of CFTR or endogenous kinase activities because basic pH independently stimulated ENaC (1) in normal ducts even when CFTR was deactivated, (2) in CF ducts that lack CFTR in the plasma membranes and (3) after blocking endogenous kinase activity with staurosporine. Considering the evidence of Na+/H+ exchange (NHE) activity as shown by the expression of mRNA and function of NHE in the basolateral membrane of the sweat duct, we postulate that changes in cytosolic Na+ ([Na+] i ) may alter cytosolic pH (pH i ) as salt loads into the cell during electrolyte absorption. These changes may play a role in coordinating the activities of ENaC and CFTR during transepithelial salt transport.

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Acknowledgments

The authors are grateful to Mr. Kirk Taylor for expert technical assistance and the numerous subjects who volunteered for skin biopsy. This study was funded by NIH-RO1 DE14352, NIH-RO1HL08042, USPHS R01 DK 51889 and the Nancy Olmsted Trust.

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Authors and Affiliations

  1. Department of Pediatrics-0831, School of Medicine, University of California–San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0831, USA

    M. M. Reddy & P. M. Quinton

  2. Department of Biological Engineering, Faculty of Life Sciences and Technology, College of Marine Life Science, Ocean University of China, 5 Yushan Road, Qindao, Shandong, 266003, People’s Republic of China

    X. F. Wang

  3. Division of Biomedical Sciences, University of California–Riverside, Riverside, CA, 92507, USA

    P. M. Quinton

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  1. M. M. Reddy
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  2. X. F. Wang
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  3. P. M. Quinton
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Correspondence to M. M. Reddy.

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Reddy, M.M., Wang, X.F. & Quinton, P.M. Effect of Cytosolic pH on Epithelial Na+ Channel in Normal and Cystic Fibrosis Sweat Ducts. J Membrane Biol 225, 1–11 (2008). https://doi.org/10.1007/s00232-008-9126-4

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  • DOI: https://doi.org/10.1007/s00232-008-9126-4

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