Effects of vigorous isometric muscle contraction on titin stiffness-related contractile properties in rat fast-twitch muscles

This study was conducted to examine the effects of an acute bout of vigorous isometric contractions on titin stiffness-related contractile properties in rat fast-twitch skeletal muscles. Intact gastrocnemius muscles were electrically stimulated in situ until the force was reduced to ∼50% of the initial force. Immediately after cessation of the stimulation, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analyses. The stimulation resulted in a decrease in the titin-based passive force. The amounts of fragmented titin were unchanged by the stimulation. Protein kinase Cα-treatment increased the passive force in stimulated fibers to resting levels. The stimulation had no effect on the maximum Ca 2+ -activated force (max Ca 2+ force) at a sarcomere length (SL) of 2.4 μm and decreased myofibrillar (my)-Ca 2+ sensitivity at 2.6-μm SL. Stretching the SL to 3.0 μm led to the augmentation of the max Ca 2+ force and my-Ca 2+ sensitivity in both rested and stimulated fibers. For the max Ca 2+ force, the extent of the increase was smaller in stimulated than in rested fibers, whereas for my-Ca 2+ sensitivity, it was higher in stimulated than in rested fibers. These results suggest that vigorous isometric contractions decrease the titin-based passive force, possibly because of a reduction in phosphorylation by protein kinase Cα, and that the decreased titin stiffness may contribute, at least in part, to muscle fatigue.