Journal article
Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na + channel
Cell (Cambridge), Vol.83(6), pp.969-978
1995
DOI: 10.1016/0092-8674(95)90212-0
PMID: 8521520
Abstract
Liddle's syndrome is an inherited form of hypertension caused by mutations that truncate the C-terminus of human epithelial Na
+ channel (hENaC) subunits. Expression of truncated β and γ hENaC subunits increased Na
+ current. However, truncation did not alter single-channel conductance or open state probability, suggesting there were more channels in the plasma membrane. Moreover, truncation of the C-terminus of the β subunit increased apical cell-surface expression of hENaC in a renal epithelium. We identified a conserved motif in the C-terminus of all three subunits that, when mutated, reproduced the effect of Liddle's truncations. Further, both truncation of the C-terminus and mutation of the conserved C-terminal motif increased surface expression of chimeric proteins containing the C-terminus of β hENaC. Thus, by deleting a conserved motif, Liddle's mutations increase the number of Na
+ channels in the apical membrane, which increases renal Na
+ absorption and creates a predisposition to hypertension.
Details
- Title: Subtitle
- Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na + channel
- Creators
- Peter M SnyderMargaret P PriceFiona J McDonaldChristopher M AdamsKenneth A VolkBernhardt G ZeiherJohn B StokesMichael J Welsh
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.83(6), pp.969-978
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0092-8674(95)90212-0
- PMID
- 8521520
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 1995
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Neurosurgery; Medicine Administration; Internal Medicine
- Record Identifier
- 9984020896102771
Metrics
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