Meeting Abstract
The timing and magnitude of muscle stimulation with respect to sinusoidal length changes can have significant effects on muscle power output. The winding filament hypothesis suggests that upon activation, titin binds to actin and winds on the thin filament, which leads to an increase in titin stiffness that varies with muscle activation and length. As a spring in active muscle, titin could store elastic energy, which may contribute to muscle force during dynamic length changes. Here, we used the mdm mouse, with a deletion in the N2A region of titin, to investigate titin’s role during in vitro work loop experiments. Soleus muscles from wildtype and mdm mice were subjected to sinusoidal length changes while stimulated at various phases with and without the addition of a single stimulus (doublet). We hypothesized that force enhancement and doublet potentiation during cyclic movements are reduced in mdm mice. In both wildtype and mdm muscles, power increased with the addition of a doublet, but the magnitude depended on the length of the muscle at the onset of activation. Both genotypes showed the largest increase in power when stimulated at the shortest lengths and the smallest increase when stimulated at the longest lengths (p < 0.0001). The increase in power was nearly twice as large in wildtype compared to mdm muscles when they were at their shortest lengths (p = 0.0006) but did not differ at the longest lengths (p = 0.19). These results are consistent with the hypothesis that upon activation, titin stiffness increases as a result of N2A-actin binding and contributes to the force, work and power of muscles during cyclic movements. This work was funded by the Anderson Endowment at Denison, an APS UGSRF award to D.E.E. and NSF IOS-1456868.
