Estudo da interação da veratrina com o musculo esqueletico por metodos histoquimicos, ultraestruturais e bioquimicos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2000

RESUMO

Veratrine, a commercial extract from the South and Central America plant Schoenocaulon officinale (Liliaceae), activates voltage-dependent Na + channels to produce persistent depolarization and an increase in sodium ion penneability in muscle fibers or nerves. The aim of this study was to investigate the effects of the veratrine aIkaloid on skeletal muscle of mice and fish. The phenotypic expression of oxidative, oxidative glycolytic and glycolytic fibers in soleus muscle (slow-twitch, with predominant1y oxidative fibers) and EDL muscle (fast-twitch, with predominant1y glycolytic fibers) of mice, and lateral muscle of tilapia were examined at various times afier intramuscular injection of veratrine. The ultrastructural changes in the muscles were analyzed by transmission electron microscoy. The veratrine effects were also examined in isolated mitochondria from mice and rats skeletal muscle, and in isolated rat liver mitochondria. In mice, oxidative and oxidative-glycolytic fibers, which are rich in mitochondria, showed decreased oxidative enzyme activity (NADH-TR reaction) afier veratrine. Glycolytic fibers, which have fewer number of mitochondria, were less sensitive to the aIkaloid. However, the oxida tive and glycolytic fibers of tilapia were more susceptible to damage by veratrine. There was a significant decrease (P=0.001) in the number oftype IIB fibers and an increase in the number of type I fibers in EDL muscle of mice (m-ATPase reaction) afier aIkaloid injection. In contrast, there was a decrease in type I and lIA fibers of the soleus muscle. Moreover, undifferentiated fibers were present in both muscles throughout the 60 min treatment. Contrarily, there were not alterations in the contractile activity of the three types of fibers present in tilapia lateral muscle up to 30 min afier aIkaloid injection, but undifferentiated fibers were seen afier 60 minutes. The myonecrotic alterations produced by veratrine included swelling of the terminal cisternae sarcoplasmic reticulum, hypercontraction of myofibrils, disorganization of sarcomeres, dissociation and/or rupture of myofilaments and mitochondrial" damage. These alterations differed in gravity and duration in different muscles. Thus, swelling of the sarcoplasmic reticulum cisternae was earlier and more prominent in EDL muscle fibers than in the soleus, and was subtle in tilapia muscle fibers. The mitochondrial alterations though were earlier and more prominent in the soleus than in the EDL. The effects of veratrine in isolated mitochondria showed that the aIkaloid uncouples oxidative phosphorylation in mice and rats skeletal muscle due to an increase in unspecific permeability transition of the inner membrane to protons. Differently, the respiratory activity on isolated liver mitochondria was inhibited afier veratrine administration. We conclude that the interaction of veratrine with muscle fibers is species-specific, muscle-specific and fiber type-specific, and that the interaction of the veratrine with mitochondrial is tissue( organ)-specific. The veratrine induced-myonecrotic alterations were attributed to the higher influx ofNa+ ions and water into cells, since they were antagonized by tetrodotoxin, a Na+ channel blocker. However, the involvement of other mechanisms, such as the mobilization of calcium ions from sarcoplasmic reticulum cisternae or mitochondria, and/or the entry oftoxin into cells cannot be ruled out

ASSUNTO(S)

veratrina musculos

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