ROLE OF INTRACELLULAR CALCIUM AND METABOLITES IN LOW-FREQUENCY FATIGUE OF MOUSE SKELETAL-MUSCLE

We have examined the extent to which prolonged reductions in low-frequ ency force (i.e., low-frequency fatigue) result from increases in intr acellular free Ca2+ concentration ([Ca2+](i)) and alterations in muscl e metabolites. Force and [Ca2+](i) were measured in mammalian single m uscle fibers in response to short,intermediate, and long series of tet ani that elevated the [Ca2+](i)-time integral to 5, 17, and 29 mu M . s, respectively. Only the intermediate and long series resulted in pro longed (>60-min) reductions in Ca2+ release and low-frequency fatigue. When fibers recovered from the long series of tetani without glucose, Ca2+ release was reduced to a greater extent and force was reduced at high and low frequencies. These findings indicate that the decrease i n sarcoplasmic reticulum Ca2+ release associated with fatigue has at l east two components: I) a metabolic component, which, in the presence of glucose, recovers within 1 h, and 2) a component dependent on the e levation of the [Ca2+](i)-time integral, which recovers more slowly It is this Ca2+-dependent component that is primarily responsible for lo w-frequency fatigue.