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A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 92(12)
- Publication Year :
- 1995
-
Abstract
- We have studied the functional consequences of a mutation in the epithelial Na+ channel that causes a heritable form of salt-sensitive hypertension, Liddle disease. This mutation, identified in the original kindred described by Liddle, introduces a premature stop codon in the channel beta subunit, resulting in a deletion of almost all of the C terminus of the encoded protein. Coexpression of the mutant beta subunit with wild-type alpha and gamma subunits in Xenopus laevis oocytes resulted in an approximately 3-fold increase in the macroscopic amiloride-sensitive Na+ current (INa) compared with the wild-type channel. This change in INa reflected an increase in the overall channel activity characterized by a higher number of active channels in membrane patches. The truncation mutation in the beta subunit of epithelial Na+ channel did not alter the biophysical and pharmacological properties of the channel--including unitary conductance, ion selectivity, or sensitivity to amiloride block. These results provide direct physiological evidence that Liddle disease is related to constitutive channel hyperactivity in the cell membrane. Deletions of the C-terminal end of the beta and gamma subunits of rat epithelial Na+ channel were functionally equivalent in increasing INa, suggesting that the cytoplasmic domain of the gamma subunit might be another molecular target for mutations responsible for salt-sensitive forms of hypertension.
- Subjects :
- Epithelial sodium channel
NEDD4L
Multidisciplinary
Sodium channel
Biology
medicine.disease
Molecular biology
Epithelium
Sodium Channels
Amiloride
Liddle Syndrome
R-type calcium channel
Xenopus laevis
Hypertension
Mutation
medicine
Oocytes
Animals
Liddle's syndrome
medicine.drug
Gamma subunit
Sequence Deletion
Research Article
Subjects
Details
- ISSN :
- 00278424
- Volume :
- 92
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....e335c7cf1e1e7d54d0a0baeea9a912eb