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

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

Результат исследований: Научные публикации в периодических изданияхтезисы


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.
Язык оригиналаанглийский
Номер статьиPP.202
Страницы (с-по)146-147
ЖурналActa Physiologica Scandinavica
Номер выпускаS718
СостояниеОпубликовано - сен 2019
СобытиеJoint Meeting of the Federation of European Physiological Societies (FEPS) and the Italian Physiological Society (SIF) - Bologna, Российская Федерация
Продолжительность: 10 сен 201913 сен 2019