ABSTRACT
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-ß-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.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Action Potentials/drug effects , Muscle Fibers, Skeletal/drug effects , Ouabain/administration & dosage , Ouabain/pharmacology , Aminoimidazole Carboxamide/administration & dosage , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Animals , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Male , Muscle Fibers, Skeletal/enzymology , Muscle Fibers, Skeletal/metabolism , Rats , Rats, Wistar , Ribonucleotides/administration & dosage , Ribonucleotides/pharmacology , Sodium-Potassium-Exchanging ATPase/metabolism , Structure-Activity RelationshipABSTRACT
AIM: To investigate the effect of application of IL-1beta on dynamics of wound healing in immunosupressed mice using electron microscopy. MATERIALS AND METHODS: Forty-five outbred adult male mice were used as a biological model. Immunosuppression was induced by administration of hydrocortisone. Using biopsy punches ("Stiefel"), 2 wounds 4 cm in diameter were inflicted to each animal in area of back part of the spine with control of their depth to superficial muscular fascia. Dynamics of changes in regenerating epidermis and identification of microbial communities were studied by electron microscopy of ultrathin sections. The speed of skin regeneration was evaluated by photometric method. Photometry of the wound was performed just after wound-inflicting operation and on 3rd, 8th, and 14th day of the experiment. RESULTS: Electron microscopy showed that IL-1beta promoted cell differentiation processes that was expressed in earlier development of protein-synthesizing organelles of newly generated spinous cells and in formation of stratum granulosum with greater number of intracellular junctions. The most expressed differences in wound regeneration were observed in the samples taken on 8th and 14th days of the experiment. CONCLUSION: Application of IL-1beta promotes wound healing under immunosuppression and accelerates purification of the wound from microorganisms preventing growth of gram-positive and gram-negative microflora as well as development of filamentous forms of micromycetes.
