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  Na,K-ATPase mutations in familial hemiplegic migraine lead to functional inactivation

Koenderink, J. B., Zifarelli, G., Yan Qiu, L., Schwarz, W., De Pont, J. J. H., Bamberg, E., et al. (2005). Na,K-ATPase mutations in familial hemiplegic migraine lead to functional inactivation. Biochimica et Biophysica Acta-Biomembranes, 1669(1), 61-68. doi:10.1016/j.bbamem.2005.01.003.

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 Creators:
Koenderink, Jan B.1, Author
Zifarelli, Giovanni2, Author           
Yan Qiu, Li1, Author
Schwarz, Wolfgang2, Author           
De Pont, Jan Joep H.H.M.1, Author
Bamberg, Ernst2, 3, Author           
Friedrich, Thomas2, Author           
Affiliations:
1Department of Biochemistry, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, The Netherlands, ou_persistent22              
2Department of Biophysical Chemistry, Max Planck Institute of Biophysics, Max Planck Society, ou_2068289              
3Johann-Wolfgang-Goethe-University Frankfurt am Main, Department of Chemical and Pharmaceutical Sciences, 60439 Frankfurt am Main, Germany, ou_persistent22              

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Free keywords: Human Na+/K+-ATPase α2-subunit; ATP1A2; Familial hemiplegic migraine type 2; Pump current; Surface expression; ATP hydrolysis
 Abstract: The Na,K-ATPase is an ion-translocating transmembrane protein that actively maintains the electrochemical gradients for Na+ and K+ across the plasma membrane. The functional protein is a heterodimer comprising a catalytic α-subunit (four isoforms) and an ancillary β-subunit (three isoforms). Mutations in the α2-subunit have recently been implicated in familial hemiplegic migraine type 2, but almost no thorough studies of the functional consequences of these mutations have been provided. We investigated the functional properties of the mutations L764P and W887R in the human Na,K-ATPase α2-subunit upon heterologous expression in Xenopus oocytes. No Na,K-ATPase-specific pump currents could be detected in cells expressing these mutants. The binding of radiolabelled [3H]ouabain to intact cells suggested that this could be due to a lack of plasma membrane expression. However, plasma membrane isolation showed that the mutated pumps are well expressed at the plasma membrane. 86Rb+-flux and ATPase activity measurements demonstrated that the mutants are inactive. Therefore, the primary disease-causing mechanism is loss-of-function of the Na,K-ATPase α2-isoform.

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Language(s): eng - English
 Dates: 2005-01-102004-08-192005-01-102005-01-262005-05-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.bbamem.2005.01.003
PMID: 15843000
 Degree: -

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Title: Biochimica et Biophysica Acta-Biomembranes
Source Genre: Journal
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Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 1669 (1) Sequence Number: - Start / End Page: 61 - 68 Identifier: ISSN: 0005-2736
CoNE: https://pure.mpg.de/cone/journals/resource/954926938702