Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility.
Binge drinking of alcohol may lead to acute alcoholic myopathy with rhabdomyolysis, which is characterized by skeletal muscle damage, elevated serum creatine kinase (CK), and myoglobinuria. This study was undertaken to test whether alcohol acts directly on the skeletal muscles to enhance the leakage of CK, and to assess the influence of fiber-type composition and repetitive contractions of the muscle on the effect of alcohol. After 4 hr of incubation in normal physiological solution at 37 degrees C, mean leakage of CK was 0.7 units/mg from isolated rat extensor digitorum longus (EDL), which has more fast-twitch glycolytic muscle fibers, and 1.2 units/mg from the soleus, which has more slow-twitch oxidative muscle fibers. Ethanol at 0.1, 0.2, and 0.5% concentrations caused significantly greater increase in leakage of CK from soleus than from EDL. In normal physiological solution, electrical stimulation at 1 Hz for 4 hr increased the leakage of CK by about the same degree in both EDL and soleus. In the presence of 0.1 and 0.2% ethanol, electrical stimulation markedly potentiated the alcohol-induced leakage of CK from both soleus and EDL. These results indicate that alcohol increases the leakage of CK by acting directly on skeletal muscle fibers, especially of the slow-twitch oxidative type, and that repeated muscle contractions potentiate the alcohol effect. These studies suggest that exercise may increase the chances of rhabdomyolysis in the alcoholics.
To assess the impairment of muscle membrane excitation, excitationcontraction (E-C) coupling, and contractility during muscle fatigue, we monitored the contracture responses of resting and fatigued muscles on exposure to high potassium and caffeine. On exposure to 140 mmol/L potassium, mouse extensor digitorum longus (EDL) developed a contracture which was 15.7% of tetanic tension before fatigue and 31.7% after fatigue, while soleus developed 59.4% contracture before and 68.8% after fatigue. Potassium causes contractures by depolarizing the muscle fiber membrane. Hence, membrane excitation is reduced in fatigued EDL and soleus. On exposure to 32 mmol/L caffeine, the contracture was 7.1% in resting EDL, 8.5% in fatigued EDL, 50.1% in resting soleus, and 43.7% in fatigued soleus. On exposure to 1 mmol/L caffeine followed by rapid cooling, the contracture was 3.0% in resting EDL, 3.2% in fatigued EDL, 21.5% in resting soleus, and 10.3% in fatigued soleus. Caffeine causes contracture by releasing Ca+ + from the sarcoplasmic reticulum. Our results indicate reduced E-C coupling attributable to reduced membrane excitation in fatigued EDL, and reduced contractility in fatigued soleus. 0 1994 John Wiley & Sons, Inc.
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