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Calcium-induced calcium release is protected from the damaging effects of fatiguing stimulation in slow- but not in fast-twitch skeletal muscles



Calcium-induced calcium release is protected from the damaging effects of fatiguing stimulation in slow- but not in fast-twitch skeletal muscles



FASEB Journal 16(5): A775



Damaging effects of fatigue are caused by the disruption of the normal excitation-contraction coupling process; calcium uptake and/or calcium release by the sarcoplasmic reticulum. By using both intact and single skinned muscle fibers, we report here for the first time that fatiguing stimulation abolishes CICR in EDL but not in soleus (SOL). Fatiguing stimulation did not affect the contractile proteins or calcium-uptake by the SR of fatigued skinned fibers from either EDL or SOL muscles. Loss of CICR in skinned muscle fibers was reflected in intact EDL muscles, since caffeine, an agent known to enhance CICR, promptly restored contractile function in fatigued EDL muscles at the end of a 30 min recovery period. In contrast, caffeine had no additional effects on the contractile function of intact fatigued SOL muscles at the end of the recovery period since they had already achieved full recovery at that time. We hypothesize that fatiguing stimulation causes oxidative modifications of the ryanodine receptor and/or its accessory proteins leading to the disruption of CICR in EDL muscles. We speculate that this does not occur in SOL muscles because of their higher intracellular levels of antioxidants.

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Accession: 034522095

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