Isoform-Specific Na,K-ATPase and Membrane Cholesterol Remodeling in the Motor Endplates in Distinct Mouse Models of Myodystrophy.

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. PMID: 32293933 [PubMed - as supplied by publisher]
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research