Alterations of the a2 Na,K-ATPase Observed in Distinct Mouse Models of Myodystrophy

V. Kravtsova , E. Bouzinova, V. Matchkov, I. Krivoi

Research output

Abstract

The Na,K-ATPase (NKA) is a membrane transporter critically important for excitability, electrogenesis and contractility of skeletal muscle, where the alpha1 and alpha2 isoforms of NKA are expressed. Mdx and Bla/J mice are the experimental models of myodystrophy, specifically of Duchenne muscular dystrophy and dysferlinopathy, respectively. The molecular mechanisms behind myodystrophy are of therapeutic importance; however the role of NKA in these dysfunctions has not previously been addressed in detail. This study examines the function of the alpha1 and alpha2 NKA isozymes in diaphragm muscle of mdx and Bla/J mice compared to control С57Bl/6 mice. We used conventional electrophysiology, quantitative PCR and Western blotting as well as confocal microscopy with cytochemistry. In both mdx and Bla/J mice muscle fiber membrane was depolarized due to specific loss of the alpha2 NKA electrogenic activity. These disturbances were most pronounced in the motor endplate membrane region, where the alpha2 NKA localization was also strongly altered. However, in contrast to Bla/J mice, the alpha2 NKA protein content as well as mRNA expression was specifically and significantly lowered only in mdx mice. Duchenne muscular dystrophy and dysferlinopathies differ fundamentally in their molecular mechanism. Nevertheless, both mdx and Bla/J mice are characterized by similar abnormalities in membrane localization and impaired function of the alpha2 NKA that can be resulted from adaptive skeletal muscle remodeling following chronic motor dysfunction. This work was supported by the Russian Science Foundation, project no. 18-15-00043.
Original languageEnglish
Article numberPP.202
Pages (from-to)146-147
JournalActa Physiologica Scandinavica
Volume227
Issue numberS718
Publication statusPublished - Sep 2019
EventJoint Meeting of the Federation of European Physiological Societies (FEPS) and the Italian Physiological Society (SIF) - Bologna
Duration: 10 Sep 201913 Sep 2019

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