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Publication year
2014Source
Biochimica et Biophysica Acta. Biomembranes, 1838, 7, (2014), pp. 1693-700ISSN
Publication type
Article / Letter to editor
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Organization
Paediatrics - OUD tm 2017
Pharmacology-Toxicology
Biochemistry (UMC)
Journal title
Biochimica et Biophysica Acta. Biomembranes
Volume
vol. 1838
Issue
iss. 7
Page start
p. 1693
Page end
p. 700
Subject
Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Sporadic hemiplegic migraine type 2 (SHM2) and familial hemiplegic migraine type 2 (FHM2) are rare forms of hemiplegic migraine caused by mutations in the Na(+),K(+)-ATPase alpha2 gene. Today, more than 70 different mutations have been linked to SHM2/FHM2, randomly dispersed over the gene. For many of these mutations, functional studies have not been performed. Here, we report the functional characterization of nine SHM2/FHM2 linked mutants that were produced in Spodoptera frugiperda (Sf)9 insect cells. We determined ouabain binding characteristics, apparent Na(+) and K(+) affinities, and maximum ATPase activity. Whereas membranes containing T345A, R834Q or R879W possessed ATPase activity significantly higher than control membranes, P796S, M829R, R834X, del 935-940 ins Ile, R937P and D999H membranes showed significant loss of ATPase activity compared to wild type enzyme. Further analysis revealed that T345A and R879W showed no changes for any of the parameters tested, whereas mutant R834Q possessed significantly decreased Na(+) and increased K(+) apparent affinities as well as decreased ATPase activity and ouabain binding. We hypothesize that the majority of the mutations studied here influence interdomain interactions by affecting formation of hydrogen bond networks or interference with the C-terminal ion pathway necessary for catalytic activity of Na(+),K(+)-ATPase, resulting in decreased functionality of astrocytes at the synaptic cleft expressing these mutants.
This item appears in the following Collection(s)
- Academic publications [238426]
- Electronic publications [122508]
- Faculty of Medical Sciences [90358]
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