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

Détails

ID Serval
serval:BIB_15DA1EF9A548
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic migraine.
Périodique
Neuromolecular medicine
Auteur⸱e⸱s
Capendeguy O., Horisberger J.D.
ISSN
1535-1084
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
6
Numéro
2-3
Pages
105-16
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
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.
Mots-clé
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
Création de la notice
24/01/2008 13:38
Dernière modification de la notice
20/08/2019 13:45
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