Fatigue of rapid and slow onset in isolated perfused rat and mouse diaphragms

Muscle fatigue was studied in the isolated perfused rat (66% oxidative fibers) and mouse (99% oxidative fibers) diaphragms. Both muscles displayed two fatigue patterns when exposed to 333-ms trains of 20-Hz stimulation. A rapid fatigue pattern appeared within each contractile train as an immediate progressive twitch-by-twitch diminution in contractility [a decrease in maximal isometric twitch tension (T) and maximal rate of T development]. An intertrain slow fatigue pattern also appeared as a progressive train-by-train diminution in contractility and an increased maximal rate of relaxation normalized to T. A reduction in the stimulatory frequency from 20 to 2 Hz caused a considerable diminution in the rapid fatigue pattern. These data suggest that rapid fatigue results from the time course of mechanical restitution, the time necessary for the Ca2+ channels of the sarcoplasmic reticulum to recover from inactivation. The slow fatigue pattern, on the other hand, is thought to be due to changes in the intracellular milieu. The difference in sensitivity of the rat and mouse diaphragms to rapid and slow fatigue is apparently related to differences in their fiber type composition. Thus, as would be expected, the mouse diaphragm, composed of only oxidative fibers, is less susceptible to slow fatigue compared with the rat diaphragm. On the other hand, it is more susceptible to rapid fatigue.