Low Extracellular Po2 Decreases Ca2+ Sensitivity During Fatigue In Single Xenopus Skeletal Muscle Fibers

Abstract

PURPOSE We examined whether reduced O2 availability in working skeletal muscle, compared to conditions when O availability is greater, involves an alteration in myofilament Ca2+ sensitivity during fatigue. METHODS Relative force (P) and cytosolic Ca2+ concentration ([Ca2+]c) were measured simultaneously in isolated single Xenopusskeletal muscle fibers (n=8) stimulated at sequentially increasing frequencies (0.25, 0.33, 0.5 and 1 contraction/sec), at an extracellular PO2 of either 21 or 159 mm Hg. Stimulation was terminated when P<50% of initial peak tension values (Po). RESULTS No significant difference (p<0.05) in P was observed between treatments during the first 2 min of contractions. At 2 min, however, a significant difference (p<0.05) in P was observed between the low PO2 treatment (P/Po=0.81±0.03) and the high (P/PO=0.89±0.02), which continued until the end of stimulation. The fatigue end-point (P/P =0.5) occurred significantly sooner during the low PO treatment (4.6±0.4 min) than the high (5.3±0.4 min). Myofilament Ca2+ sensitivity was determined by examining the ratio of relative peak [Ca2+]c to relative force (i.e, [Ca2+]c /P). No difference in [Ca2+]c /P was observed between the two treatments during the initial 2 min. However, beyond this two-minute time point, a significant difference in [Ca2+] /P was observed between the low PO2 condition (1.16±0.03) and the high (1.09±0.03), showing a diminished force development for a given [Ca2+]c in the low extracellular PO2condition. CONCLUSIONS These results suggest that in contracting, single Xenopusskeletal muscle fibers, the development of fatigue during conditions of limited oxygen availability is associated with a decrease in myofilament Ca2+ sensitivity when compared to conditions of greater oxygen availability. Supported by NIH Grant AR40155