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Ouabain Modulates t...
Ouabain Modulates the Functional Interaction Between Na,K-ATPase and NMDA Receptor.
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- Akkuratov, Evgeny E. (author)
- KTH,Biofysik,Science for Life Laboratory, SciLifeLab
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Westin, Linda (author)
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Vazquez-Juarez, Erika (author)
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de Marothy, Minttu (author)
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- Melnikova, Aleksandra K (author)
- Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia, 119234
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- Blom, Hans, 1968- (author)
- KTH,Biofysik,Science for Life Laboratory, SciLifeLab
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- Lindskog, Maria (author)
- Karolinska Institutet
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- Brismar, Hjalmar (author)
- Karolinska Institutet,KTH,Biofysik,Science for Life Laboratory, SciLifeLab
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- Aperia, Anita (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2020-07-10
- 2020
- English.
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In: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 57:10, s. 4018-4030
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Abstract
Subject headings
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- The N-methyl-D-aspartate (NMDA) receptor plays an essential role in glutamatergic transmission and synaptic plasticity and researchers are seeking for different modulators of NMDA receptor function. One possible mechanism for its regulation could be through adjacent membrane proteins. NMDA receptors coprecipitate with Na,K-ATPase, indicating a potential interaction of these two proteins. Ouabain, a mammalian cardiotonic steroid that specifically binds to Na,K-ATPase and affects its conformation, can protect from some toxic effects of NMDA receptor activation. Here we have examined whether NMDA receptor activity and downstream effects can be modulated by physiological ouabain concentrations. The spatial colocalization between NMDA receptors and the Na,K-ATPase catalytic subunits on dendrites of cultured rat hippocampal neurons was analyzed with super-resolution dSTORM microscopy. The functional interaction was analyzed with calcium imaging of single hippocampal neurons exposed to 10 μM NMDA in presence and absence of ouabain and by determination of the ouabain effect on NMDA receptor-dependent long-term potentiation. We show that NMDA receptors and the Na,K-ATPase catalytic subunits alpha1 and alpha3 exist in same protein complex and that ouabain in nanomolar concentration consistently reduces the calcium response to NMDA. Downregulation of the NMDA response is not associated with internalization of the receptor or with alterations in its state of Src phosphorylation. Ouabain in nanomolar concentration elicits a long-term potentiation response. Our findings suggest that ouabain binding to a fraction of Na,K-ATPase molecules that cluster with the NMDA receptors will, via a conformational effect on the NMDA receptors, cause moderate but consistent reduction of NMDA receptor response at synaptic activation.
Subject headings
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- Calcium
- LTP
- NMDAR
- Na
- K-ATPase
- Ouabain
- Protein-protein interaction
- Super-resolution microscopy
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Akkuratov, Evgen ...
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Westin, Linda
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Vazquez-Juarez, ...
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de Marothy, Mint ...
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Melnikova, Aleks ...
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Blom, Hans, 1968 ...
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show more...
-
Lindskog, Maria
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Brismar, Hjalmar
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Aperia, Anita
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biophysics
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Molecular Neurob ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet