Meeting Abstract
A single stimulus (doublet) added to a train of stimuli increases the force output of a muscle. However, current theories used to explain muscle contraction fail to accurately predict muscle force during doublet potentiation. Recent work has suggested that the sarcomeric protein, titin, may play a role. Here, we investigated the role of titin in doublet potentiation by using the muscular dystrophy with myositis (mdm) mouse, which is characterized by a deletion in the N2A region of the titin gene. Previous research suggests that upon activation, the N2A region binds to the thin filaments, which increases titin stiffness. We hypothesized that the absence of N2A-thin filament binding in mdm muscles reduces doublet potentiation. Using a servomotor force lever, we measured doublet potentiation at different muscle lengths in vitro from the soleus and extensor digitorum longus (EDL) muscles of wildtype and mdm mice. Potentiation was 20% lower in mdm than in wildtype soleus at all lengths (p = 0.04). In contrast to soleus, there was no difference in potentiation between wildtype and mdm EDL muscles (p = 0.7). In addition, potentiation was greater at optimum length than on the descending limb of the force-length relationship in both soleus and EDL wildtype muscles, but mdm muscles did not show length dependence. Results from soleus muscles are consistent with the hypothesis that titin plays a role in doublet potentiation and that the lack of titin-actin binding in mdm soleus muscles reduces doublet potentiation of muscle force. Differences in myosin isoforms, calcium flux, or titin isoforms, alone or in combination, may contribute to the observed differences between soleus and EDL in doublet potentiation.
