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Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function

Nature volume 402, pages 301–304 (1999)Cite this article

Abstract

It is increasingly being recognized that cells coordinate the activity of separate ion channels that allow electrolytes into the cell. However, a perplexing problem in channel regulation has arisen in the fatal genetic disease cystic fibrosis, which results from the loss of a specific Cl- channel (the CFTR channel) in epithelial cell membranes1. Although this defect clearly inhibits the absorption of Na+ in sweat glands2,3, it is widely accepted that Na+ absorption is abnormally elevated in defective airways in cystic fibrosis4,5. The only frequently cited explanation for this hypertransport is that the activity of an epithelial Na+ channel (ENaC) is inversely related to the activity of the CFTR Cl- channel5,6,7. However, we report here that, in freshly isolated normal sweat ducts, ENaC activity is dependent on, and increases with, CFTR activity. Surprisingly, we also find that the primary defect in Cl- permeability in cystic fibrosis8 is accompanied secondarily by a Na+ conductance in this tissue that cannot be activated. Thus, reduced salt absorption in cystic fibrosis is due not only to poor Cl- conductance but also to poor Na+ conductance.

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Figure 1: Effect of cAMP and ATP activation of CFTR Cl- conductance (gCFTR) on amiloride-sensitive epithelial Na+ conductance (gENaC).
Figure 2: Effect of stimulating gCFTR with cGMP and ATP on gENaC.
Figure 3: Effect of stimulating gCFTR with GTP-γ-S and ATP on gENaC.
Figure 4: Failure of stimulation to increase gENaC† in the absence of functional CFTR.

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Acknowledgements

We thank K. Taylor for technical assistance. This work was funded by grants from the Nancy McCracken Endowment, the Cystic Fibrosis Foundation and the USPHS National Institutes of Health.

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  1. Department of Pediatrics-0831, University of California, San Diego, School of Medicine, La Jolla, 92093-0831, California, USA

    M. M. Reddy, M. J. Light & P. M. Quinton

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  1. M. M. Reddy
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  2. M. J. Light
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  3. P. M. Quinton
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Correspondence to P. M. Quinton.

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Reddy, M., Light, M. & Quinton, P. Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function. Nature 402, 301–304 (1999). https://doi.org/10.1038/46297

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