ArticleActa myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology2016
Eplerenone repolarizes muscle membrane through Na,K-ATPase activation by Tyr10 dephosphorylation.
Article in Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.The Journal of general physiology · 2022Article
- Phosphorylation of NaThe Journal of membrane biology · 2021Article
- Skeletal muscle CaPflugers Archiv : European journal of physiology · 2020Review
- Current and emerging therapies in Becker muscular dystrophy (BMD).Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2019Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eplerenone, an aldosterone antagonist, repolarizes muscle membrane in-vitro and increases strength in-vivo in channelopathies. In Duchenne dystrophy, it is administered for cardiomyopathy. We studied its mechanism of action on skeletal muscle to test its suitability for increasing strength in Duchenne dystrophy. Using membrane potential measurements, quantitative PCR, ELISA, and Western blots, we examined the effects of eplerenone on skeletal muscle Na,K-ATPase. The repolarizing effect of eplerenone in muscle fibres was counteracted by oubain, an ATPase blocker. In our experiment, ATPA1A mRNA and total ATPase protein were not elevated. Instead, Tyr10 of the α1 subunit was dephosphorylated which would agree with ATPase activation. Dephosporylation of the coupled Akt kinase corroborated our findings. We conclude that eplerenone repolarizes muscle membrane by Na,K-ATPase activation by dephosphorylation at Tyr10. Since ATPase protein is known to be compensatorily increased in Duchenne patients without activity change, eplerenone treatment may be beneficial.
Indexed as
Identifiers
28344437PMC5343744W2963409132What OpenQuestion holds
Registered trials
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