Intracellular Calcium Handling and Not Contraction Type Determines Task-Dependent Skeletal Muscle Fatigue

Aim: This study compared skeletal muscle fatigue induced by different contraction-types to determine whether repeated shortening contractions cause greater fatigability via larger reductions in sarcoplasmic reticulum Ca²⁺ release than repeated isometric contractions. A secondary objective was to assess whether fatigability differs when initial shortening and isometric contraction forces are matched between tasks. Methods: Single intact flexor digitorum brevis fibers from female C57Bl/6 mice were dissected and loaded with indo-1 AM to measure myoplasmic free [Ca²⁺]([Ca²⁺]_i). Fibers were assigned to one of three protocols: isometric, shortening, or force-matched isometric. Fatigue was induced by stimulating fibers with tetani (300 ms) every 2 s for 50 contractions. Isometric and shortening groups were stimulated at 70 Hz, with shortening velocity set to achieve peak power; the force-matched isometric group was stimulated at ∼31 Hz (25-45 Hz) to match the initial force of shortening contractions. Every tenth contraction during all fatigue protocols, force and [Ca²⁺]_i were assessed with isometric as well as shortening contractions to compare fatigability across tasks using identical contraction types. Results: When fatigued by 70 Hz tetani, shortening and isometric contractions produced similar declines in force, tetanic [Ca²⁺]_i, and resting [Ca²⁺]_i. However, when compared with force-matched isometric contractions, shortening contractions resulted in greater fatigue-induced force loss, larger reductions in tetanic [Ca²⁺]_i, and greater increases in resting [Ca²⁺]_i (p < 0.05). Conclusion: Contraction type-dependent differences in skeletal muscle fatigue are driven primarily by differences in intracellular Ca²⁺ handling rather than the contraction type as such.