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Chronic ouabain prevents na,k-atpase dysfunction and targets ampk and il-6 in disused rat soleus muscle

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  • Violetta V. Kravtsova, St. Petersburg State University
  • ,
  • Inna I. Paramonova, Russian Academy of Sciences
  • ,
  • Natalia A. Vilchinskaya, Russian Academy of Sciences
  • ,
  • Maria V. Tishkova, St. Petersburg State University
  • ,
  • Vladimir V. Matchkov
  • Boris S. Shenkman, Russian Academy of Sciences
  • ,
  • Igor I. Krivoi, St. Petersburg State University

Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is char-acteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis and prevents its dis-use-induced disturbances. Isolated soleus muscles from rats intraperitoneally injected with oua-bain alone or subsequently exposed to muscle disuse by 6-h hindlimb suspension (HS) were stud-ied. Conventional electrophysiology, Western blotting, and confocal microscopy with cytochemis-try were used. Acutely applied 10 nM ouabain hyperpolarized the membrane. However, a single injection of ouabain (1 µg/kg) prior HS was unable to prevent the HS-induced membrane depo-larization. Chronic administration of ouabain for four days did not change the α1 and α2 Na,K-ATPase protein content, however it partially prevented the HS-induced loss of the Na,K-ATPase electrogenic activity and sarcolemma depolarization. These changes were associated with increased phosphorylation levels of AMP-activated protein kinase (AMPK), its substrate ac-etyl-CoA carboxylase and p70 protein, accompanied with increased mRNA expression of inter-leikin-6 (IL-6) and IL-6 receptor. Considering the role of AMPK in regulation of the Na,K-ATPase, we suggest an IL-6/AMPK contribution to prevent the effects of chronic ouabain under skeletal muscle disuse.

Original languageEnglish
Article number3920
JournalInternational Journal of Molecular Sciences
Number of pages18
Publication statusPublished - Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    Research areas

  • AMP-activated protein kinase, Hindlimb suspension, Na,K-ATPase isozymes, Ouabain, Resting membrane potential, Skeletal muscle

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