Although the precise mechanisms underlying the dysfunction of sarcoplasmic reticulum (SR) that occurs during skeletal muscle fatigue remain obscure, it has been hypothesized that it may be attributable to oxidation of critical sulfhydryl groups residing in SR Ca²⁺-ATPase protein by endogenously produced reactive oxygen species. In order to test this hypothesis, SR Ca²⁺-ATPase activities in the absence or presence of the disulfide reducing agent, dithiothreitol (DTT), were examined in muscle homogenates of the soleus muscles (SQL) and the superficial portions of the vastus lateralis muscles (VS) from the rat subjected to exhaustive running at 50 m/min on a 10% grade. Immediately after exercise, the catalytic activity of SR Ca²⁺-ATPase was significantly depressed in VS, but not in SQL. The loss of SR Ca²⁺-ATPase activity observed in VS was fully recovered after treatment with DTT (1 mM) . These recovery effects of a potent disulfide reducing agent suggest that important proteins of SR Ca²⁺-ATPase may be oxidized during high-intensity exercise and that the onset of muscular fatigue may be delayed by the improved function of the cellular antioxidant

Effects of short-term, high-intensity and long-term, moderate-intensity exercise on biochemically assessed sarcoplasmic reticulum (SR) ATPase protein were analyzed in muscle homogenates of the rat after treadmill runs to exhaustion (avg, time to exhaustion 2 min 48 sec and 1 h 29 min, respectively) . The exercise-induced changes in SR Ca²⁺ -ATPase activity were muscle type-specific. After short-term exercise, a decrease in the activity occurred in the soleus muscle and the superficial region of the vastus lateralis muscle whereas long-term exercise depressed the rate of ATP hydrolysis in the soleus muscle and the deep region of the vastus lateralis muscle. The concentration of fluorescein isothiocyanate, a competitor at the ATP-binding site, for 50% inhibition of SR Ca²⁺ -ATPase activity fluctuated only in the soleus muscle subjected to short-term exercise ; it was increased by 31%. This change occurring in the soleus muscle would elevate SR Ca²⁺ -ATPase activity at a given concentration of ATP. The results presented here suggest that acute short-term exercise to exhaustion may exert a remarkably inhibitory factor on SR Ca²⁺ -ATPase protein of slow-twitch muscle, which can overcome the positive effect probably arising from the phosphorylation of the phospholamban.

This study examined the impact of acute high-intensity exercise on the rate of Ca²⁺uptake and release and Ca²⁺-stimulated adenosine triphosphatase (ATPase) activity of the sarcoplasmic reticulum (SR) in the soleus muscle (SOL) and the superficial region of the vastus lateralis muscle (VS) of rats. The animals were run on a 10% grade at 50 m/min of a motorized treadmill until fatigued (The average time to exhaustion was 306 sec.) . At exhaustion, glycogen concentrations were 65% and 85% less in the SOL and VS, respectively. The rate of Ca²⁺release induced by 4-chloro-m-cresol was un-changed in fatigued SOL and VS. The rate of Ca²⁺uptake stimulated by adenosine triphosphate (ATP) was significantly lower following exercise in VS but not in SOL. This lower rate observed in VS was paralleled by decreased catalytic activity of SR Ca²⁺-ATPase. The rate of Ca2+ uptake measured using adenosine diphosphate and phosphocreatine, as substrate was lower than that of ATP in fatigued VS. These findings suggest that, in fast-twitch muscles, high-intensity exercise not only reduces SR Ca²⁺-ATPase activity but also elicits a decrease in creatine kinase activity, probably resulting from nitric oxide that is produced during exercise.