Meeting Abstract
The goal of predicting how muscle force changes during natural cyclic movements remains elusive. The sarcomeric protein, titin, has been suggested to play a role in a number of muscle properties that influence muscle work during cyclic movements. However, the role of titin remains to be elucidated. We used the muscular dystrophy with myositis (mdm) mouse, with a deletion in the N2A region of titin to investigate titin’s role during in vitro work loop experiments. Previous research suggests that upon activation, the N2A region binds to actin, which increases titin stiffness. We hypothesized that the absence of N2A-actin binding in (mdm) muscles reduces force enhancement and doublet potentiation during cyclic movements. Using a servomotor force lever, we measured in vitro force and work of soleus and EDL muscles from wildtype and (mdm) mice. Muscles were subjected to sinusoidal length changes at a strain amplitude of ±5%Lo while phasically stimulated at submaximal frequencies. Muscle force and work were compared with and without a doublet added to the train of stimuli. In wildtype soleus and EDL muscles, the addition of a single stimulus increased force throughout the entire stretch-shortening cycle. Work increased by 50% in wildtype soleus and 30% in wildtype EDL. In contrast, (mdm) soleus and EDL muscles showed little increase in force upon activation during stretch, and the work was the same with and without a doublet. These results are consistent with the hypothesis that upon activation, titin stiffness increases as a result of N2A-actin binding and contributes to active force and work of muscles during cyclic movements. In addition, these results demonstrate the importance of the (mdm) mouse as a model system for understanding how activation and applied forces interact to determine muscle force and work.
