Aarhus Universitets segl

English

Du er her: AU » Om AU » Organisation » Isoform-specific Na,K-ATPase and membrane cholesterol rem...

Om AU

Isoform-specific Na,K-ATPase and membrane cholesterol remodeling in motor endplates in distinct mouse models of myodystrophy

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

DOI

  • Violetta V Kravtsova, St. Petersburg State University
    • ,
  • Elena V Bouzinova
  • Alexander V Chibalin, Tomsk State University
    • ,
  • Vladimir V Matchkov
  • Igor I Krivoi, St. Petersburg State University

Na,K-ATPase is a membrane transporter critically important for skeletal muscle function. Mdx and Bla/J mice are the experimental models of Duchenne muscular dystrophy and dysferlinopathy. The molecular mechanism behind myodystrophy is of therapeutic importance; however, the detailed role of Na,K-ATPase in these dysfunctions has not previously been addressed. This study examines the function of the α1 and α2 Na,K-ATPase isozymes in diaphragm and soleus muscles from mdx and Bla/J mice compared to control С57Bl/6 mice. Conventional electrophysiology, quantitative PCR and Western blotting, co-immunoprecipitation as well as confocal microscopy with cytochemistry were used. In diaphragm muscle fibers from mdx and Bla/J mice plasma membrane was depolarized due to specific loss of the α2 Na,K-ATPase electrogenic activity, which was more pronounced in the junctional (motor endplate) region; the a2 Na,K-ATPase abundance decrease and membrane cholesterol re-distribution were observed throughout the sarcolemma. However, the α2 Na,K-ATPase protein content as well as mRNA expression were specifically and significantly reduced only in mdx mice. FXYD1 (an auxiliary subunit, which modulates Na,K-ATPase activity) abundance and its association with the α2 Na,K-ATPase were decreased in both mouse models of myodystrophy, presumably as response to impaired functioning of the enzyme. Soleus muscles from mdx and Bla/J mice demonstrated difference in the pattern of the α2 Na,K-ATPase and cholesterol abnormalities compared to diaphragm muscles. Our findings indicate that these distinct mouse models of myodystrophy are characterized by α2 Na,K-ATPase and membrane cholesterol impairments, which can be a result of adaptive skeletal muscle remodeling under chronic motor dysfunction.

OriginalsprogEngelsk
TidsskriftAmerican journal of physiology. Cell physiology
Vol/bind318
Nummer5
Sider (fra-til)C1030-C1041
Antal sider12
ISSN0363-6143
DOI
StatusUdgivet - maj 2020

Se relationer på Aarhus Universitet Citationsformater

ID: 185062673