Journal article
Liddle’s syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na+ channel to the cell surface
The Journal of clinical investigation, Vol.105(1), pp.45-53
01/01/2000
DOI: 10.1172/JCI7869
PMCID: PMC382584
PMID: 10619860
Abstract
The epithelial Na
+
channel (ENaC) plays a critical role in Na
+
absorption, and mutations in this channel cause diseases of Na
+
homeostasis, including a genetic form of hypertension (Liddle’s syndrome). To investigate cAMP-mediated stimulation of ENaC, α, β, and γENaC were coexpressed in Fischer rat thyroid epithelia to generate apical Na
+
channels and transepithelial Na
+
current. cAMP agonists stimulated Na
+
current by 70%. Following covalent modification of cysteines introduced into ENaC, cAMP increased the rate of appearance of unmodified channels at the cell surface. In addition, cAMP increased the fluorescent labeling of ENaC at the apical cell surface. Inhibition of vesicle trafficking by incubating epithelia at 15°C prevented the cAMP-mediated stimulation of ENaC. These results suggest that cAMP stimulates Na
+
absorption in part by increasing translocation of ENaC to the cell surface. Stimulation of ENaC by cAMP was dependent on a sequence (PPPXY) in the COOH terminus of each subunit. This sequence is the target for mutations that cause Liddle’s syndrome, suggesting that cAMP-mediated translocation of ENaC to the cell surface is defective in this genetic form of hypertension.
Details
- Title: Subtitle
- Liddle’s syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na+ channel to the cell surface
- Creators
- Peter M Snyder - 200K Eckstein Medical Research Building, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. E-mail
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.105(1), pp.45-53
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI7869
- PMID
- 10619860
- PMCID
- PMC382584
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 01/01/2000
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
- Record Identifier
- 9984025678302771
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