Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic migraine.

Details

Serval ID
serval:BIB_15DA1EF9A548
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic migraine.
Journal
Neuromolecular medicine
Author(s)
Capendeguy O., Horisberger J.D.
ISSN
1535-1084
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
6
Number
2-3
Pages
105-16
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Familial hemiplegic migraine type 2, an autosomal dominant form of migraine with aura, has been associated with four distinct mutations in the alpha2-subunit of the Na+,K+-ATPase. We have introduced these mutations in the alpha2-subunit of the human Na+,K+-ATPase and the corresponding mutations in the Bufo marinus alpha1-subunit and studied these mutants by expression in Xenopus oocyte. Metabolic labeling studies showed that the mutants were synthesized and associated with the beta-subunit, except for the alpha2HW887R mutant, which was poorly synthesized, and the alpha1BW890R, which was partially retained in the endoplasmic reticulum. [3H]ouabain binding showed the presence of the alpha2HR689Q and alpha2HM731T at the membrane, whereas the alpha2HL764P and alpha2HW887R could not be detected. Functional studies with the mutants of the B. marinus Na+,K+-ATPase showed a reduced or abolished electrogenic activity and a low K+ affinity for the alpha1BW890R mutant. Through different mechanisms, all these mutations result in a strong decrease of the functional expression of the Na+,K+-pump. The decreased activity in alpha2 isoform of the Na+,K+-pump expressed in astrocytes seems an essential component of hemiplegic migraine pathogenesis and may be responsible for the cortical spreading depression, which is one of the first events in migraine attacks.
Keywords
Animals, Female, Hemiplegia, Humans, Migraine Disorders, Models, Molecular, Mutagenesis, Site-Directed, Mutation, Oocytes, Ouabain, Protein Conformation, Protein Subunits, Sodium-Potassium-Exchanging ATPase, Xenopus laevis
Pubmed
Web of science
Create date
24/01/2008 12:38
Last modification date
20/08/2019 12:45
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