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Low Ouabain Doses and AMP-Activated Protein Kinase as Factors Supporting Electrogenesis in Skeletal Muscle

V. V. Kravtsova1, N. A. Vilchinskaya2, V. L. Rozlomii1, B. S. Shenkman2, and I. I. Krivoi1,a*

1St. Petersburg State University, Department of General Physiology, 199034 St. Petersburg, Russia

2Institute of Biomedical Problems, Laboratory of Myology, Russian Academy of Sciences, 123007 Moscow, Russia

* To whom correspondence should be addressed.

Received February 11, 2019; Revised May 24, 2019; Accepted June 7, 2019
Many motor disorders are associated with depolarization of the membrane of skeletal muscle fibers due to the impaired functioning of Na,K-ATPase. Here, we studied the role of ouabain (specific Na,K-ATPase ligand) and AMP-activated protein kinase (key regulator of muscle metabolism) in the maintenance of muscle electrogenesis; the levels of these endogenous factors are directly related to the motor activity. After 4-day intraperitoneal administration of ouabain (1 µg/kg daily), a hyperpolarization of sarcolemma was registered in isolated rat diaphragm muscles due to an increase in the electrogenic activity of Na,K-ATPase. In acute experiments, addition of nanomolar ouabain concentrations to the bathing solution resulted in the muscle membrane hyperpolarization within 15 min. The effect of ouabain reversed to membrane depolarization with the increase in the external potassium concentration. It is possible that Na,K-ATPase activation by ouabain may be regulated by such factors as specific subcellular location, interaction with molecular partners, and changes in the ionic balance. Preventive administration of the AMP-activated protein kinase activator AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside; 400 mg/kg body weight daily for 7 days) in chronic experiments resulted in the stabilization of the endplate structure and abolishment of depolarization of the rat soleus muscle membrane caused by the motor activity cessation. The obtained data can be useful for creating approaches for correction of muscle dysfunction, especially at the early stages, prior to the development of muscle atrophy.
KEY WORDS: skeletal muscle, motor activity, ouabain, Na,K-ATPase, AMP-activated protein kinase

DOI: 10.1134/S0006297919090116