Meeting Abstract

39.3  Sunday, Jan. 5 08:30  Understanding how motor commands and applied forces interact to determine muscle force output. NISHIKAWA, KC*; MONROY, JA; PACE, CM; Northern Arizona University; Denison University; Northern Arizona University Kiisa.Nishikawa@nau.edu

The goal of predicting how muscle forces change during natural movements remains elusive. Muscle models perform poorly at predicting muscle force during stretch or shortening, as well as in doublet potentiation and work-loop experiments. Yet these properties have crucial implications for understanding motor control. Our goal is to explore the ability of the winding filament hypothesis to inform our understanding of muscle force output. We used the muscular dystrophy with myositis (mdm) mouse, with a 779 bp deletion in the N2A region of the titin gene, to test the hypothesis that titin contributes to active force in doublet potentiation and work loop experiments. We performed doublet potentiation, isovelocity stretch and shortening, and work-loop experiments in soleus muscles from wild type and mdm mice. Doublet potentiation was 20% lower in mdm than in wild type soleus. Active force enhancement was lower and passive force enhancement was higher in mdm than in wild type soleus. In work loop experiments, force increases steeply upon activation during stretch and a single added stimulus greatly increases force during active stretch in wild type soleus. The additional force persists throughout the entire cycle, and disappears only upon return to the starting length. The doublet stimulus increases muscle work per cycle by 50%. Soleus muscles from mdm mice showed little increase in force upon activation during stretch, and the work per cycle was the same with and without the doublet. These results suggest that titin contributes to dynamic force output of active muscle, and demonstrate that the mdm mouse is an important model system for understanding how motor commands and applied forces interact to determine muscle force output.