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 dis played two fatigue patterns when exposed to 333-ms trains of 20-Hz sti mulation. A rapid fatigue pattern appeared within each contractile tra in as an immediate progressive twitch-by-twitch diminution in contract ility [a decrease in maximal isometric twitch tension (T) and maximal rate of T development]. An intertrain slow fatigue pattern also appear ed as a progressive train-by-train diminution in contractility and an increased maximal rate of relaxation normalized to T. A reduction in t he stimulatory frequency from 20 to 2 Hz caused a considerable diminut ion in the rapid fatigue pattern. These data suggest that rapid fatigu e results from the time course of mechanical restitution, the time nec essary for the Ca2+ channels of the sarcoplasmic reticulum to recover from inactivation. The slow fatigue pattern, on the other hand, is tho ught to be due to changes in the intracellular milieu. The difference in sensitivity of the rat and mouse diaphragms to rapid and slow fatig ue is apparently related to differences in their fiber type compositio n. Thus, as would be expected, the mouse diaphragm, composed of only o xidative fibers, is less susceptible to slow fatigue compared with the rat diaphragm. On the other hand, it is more susceptible to rapid fat igue.