Impairment of Ca2+ release in single Xenopus muscle fibers fatigued at varied extracellular Po-2

We tested the hypothesis that the mechanisms involved in the more rapid ons et of fatigue when O-2 availability is reduced in contracting skeletal musc le are similar to those when O-2 availability is more sufficient. Two serie s of experiments were performed in isolated, single skeletal muscle fibers from Xenopus laevis. First, relative force and free cytosolic Ca2+ concentr ations ([Ca2+](c)) were measured simultaneously in single fibers (n = 6) st imulated at increasing frequencies (0.25, 0.33, 0.5, and 1 Hz) at an extrac ellular Po-2 of either 22 or 159 Torr. Muscle fatigue (force = 50% of initi al peak tension) occurred significantly sooner (P < 0.05) during the low- ( 237 +/- 40 s) vs. high-Po-2 treatments (280 +/- 38 s). Relative [Ca2+](c) w as significantly decreased from maximal values at the fatigue time point du ring both the high- (72 +/- 4%) and low-Po-2 conditions (78 +/- 4%), but no significant difference was observed between the treatments. In the second series of experiments, using the same stimulation regime as the first, fibe rs (n = 6) exposed to 5 mM caffeine immediately after fatigue demonstrated an immediate but incomplete relative force recovery during both the low- (8 9 +/- 4%) and high-Po-2 treatments (82 +/- 3%), with no significant differe nce between treatments. Additionally, there was no significant difference i n relative [Ca2+](c) between the high-(100 +/- 12% of prefatigue values) an d low-Po-2 treatments (108 +/- 12%) on application of caffeine. These resul ts suggest that in isolated, single skeletal muscle fibers, the earlier ons et of fatigue that occurred during the low-extracellular Po-2 condition was modulated through similar pathways as the fatigue process during the high and involved a decrease in relative peak [Ca2+](c).