TY - JOUR

T1 - Low Ouabain Doses and AMPActivated Protein Kinase as Factors Supporting Electrogenesis in Skeletal Muscle

AU - Kravtsova, V.V.

AU - Vilchinskaya, N.A.

AU - Rozlomii, V.L.

AU - Shenkman, B.S.

AU - Krivoi, I.I.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Many motor disorders are associated with depolarization of the membrane of skeletal muscle fibers due to the impaired functioning of Na,KATPase. Here, we studied the role of ouabain (specific Na,KATPase ligand) and AMPactivated 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 4day 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,KATPase. 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,KATPase 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 AMPactivated protein kinase activator AICAR (5aminoimidazole4car boxamide1βDribofuranoside; 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.

AB - Many motor disorders are associated with depolarization of the membrane of skeletal muscle fibers due to the impaired functioning of Na,KATPase. Here, we studied the role of ouabain (specific Na,KATPase ligand) and AMPactivated 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 4day 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,KATPase. 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,KATPase 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 AMPactivated protein kinase activator AICAR (5aminoimidazole4car boxamide1βDribofuranoside; 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.

KW - AMP-activated protein kinase

KW - Na,K-ATPase

KW - motor activity

KW - ouabain

KW - skeletal muscle

KW - STIMULATION

KW - SENSITIVITY

KW - RECEPTOR

KW - MODEL

KW - CARDIOTONIC STEROIDS

KW - HUMAN ENDOTHELIAL-CELLS

KW - NA-K-ATPASE

KW - NA+,K+-ATPASE ACTIVITY

KW - Na

KW - K-ATPase

KW - EXPRESSION

KW - SUBUNIT

UR - http://www.scopus.com/inward/record.url?scp=85073015527&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/low-ouabain-doses-ampactivated-protein-kinase-factors-supporting-electrogenesis-skeletal-muscle

U2 - 10.1134/S0006297919090116

DO - 10.1134/S0006297919090116

M3 - Article

VL - 84

SP - 1085

EP - 1092

JO - Biochemistry (Moscow)

JF - Biochemistry (Moscow)

SN - 0006-2979

IS - 9

ER -