Meeting Abstract
Muscle function during submaximal activation is seldom studied, yet is more similar to in vivo muscle function than maximal activation. For skeletal muscle, the force-length relationship shifts to longer lengths in submaximal, compared to maximal, activation conditions. Length-dependent calcium effects, specifically an increase in calcium sensitivity with increasing sarcomere length, have historically been suggested as the cause of this shift in the force-length relationship. Recent evidence suggests that the titin protein may also play a role in activation-dependent muscle properties through a length-dependent structural re-arrangement of the thick filaments. To evaluate a possible role for titin in activation dependent properties, we studied muscles from mice carrying the muscular dystrophy with myositis (mdm) mutation, which have a small titin deletion in the I-band region. For mdm and wild type soleus and EDL muscles, we measured the force-length relationships during maximal (tetanus) and submaximal (twitch) activation. We then used skinned fibers to evaluate the length-dependence of calcium sensitivity(LDC). Our results demonstrate that in contrast to wild type muscles, which showed a shift to longer optimal lengths during twitch contractions, the force-length relationship displayed the same optimum length for twitch and tetanic contractions in mdm muscles. However, in skinned fibers, the length-dependence of calcium sensitivity was similar in mdm and wild type fibers. These results suggest that the titin deletion alters activation-dependent properties without affecting the LDC. Therefore, some mechanism other than LDC is responsible for the absence of an activation-dependent shift in the force-length relationship in mdm muscles. Uncovering how this titin deletion affects activation dependent properties will be the subject of future study.
