Hypoxia and fatigue-induced modification of function and proteins in intact and skinned murine diaphragm muscle

Fatigue studies of isolated, intact muscles typically utilize solutions sat urated with O-2. However, under in vivo fatiguing conditions, less oxygen i s delivered to the muscles and they actually experience hypoxia. No studies to date have correlated the effects of acute hypoxia on the isometric cont ractile properties of intact muscles, skinned Fibers isolated from the same muscles, and the cellular content of specific muscle proteins Therefore, w e have studied the effects of in vitro acute hypoxia on the fatigability of intact diaphragm muscle strips and on the isometric contractile properties of single Triton-skinned fibers isolated from control and hypoxic diaphrag m muscles. We found that hypoxia and fatiguing stimulation per sc affect th e tetanic force of intact muscle strips without exhibiting any significant deleterious effects on the Calcium-activated force of skinned muscle fibers dissected from the intact muscles. In contrast, fatiguing stimulation unde r hypoxic conditions decreased both the tetanic: force of muscle strips and the calcium-activated force of skinned muscle fibers. Gel electrophoresis of muscles subjected to hypoxia and hypoxic-fatigue revealed th;it there is a significant reduction in three protein bands when compared to control mu scles. Protein modification may be the underlying mechanism of muscle fatig ue under physiologic conditions.