Meeting Abstract
P2-22 Doublet potentiation in soleus muscles from Ttn ?112-158 mice with a large deletion to PEVK titin Bassett, J/B*; Hurley , K/L; Monroy , J/A; Claremont Colleges jbassett22@cmc.edu
Doublet potentiation is the increase in muscle force with the addition of a pair of stimuli, called a doublet, at the beginning of a stimulus train. Current theories used to explain muscle contraction fail to accurately predict muscle force during doublet stimulation. Recent work suggests that the muscle protein titin may play a role. Here, we investigated the role of the PEVK region of titin in doublet potentiation. The PEVK region is known to contribute to passive muscle force and muscles that express titin isoforms with shorter, stiffer PEVK segments have higher passive stiffness. We measured doublet potentiation in soleus muscles from the Ttn ?112-158 mouse characterized by a 75% deletion of PEVK titin and higher passive stiffness. We hypothesized that doublet potentiation is greater in Ttn ?112-158 than wild-type muscles due to increased stiffness of PEVK titin in Ttn ?112-158 muscles. Using a servomotor force lever, we measured doublet potentiation during isometric contraction at different muscle lengths from the soleus muscles of wild type and Ttn ?112-158 mice. Doublet stimulation resulted in a 23% greater increase in peak muscle force and a 12% greater increase in the force-time integral in Ttn ?112-158 than wild type muscles at short muscle lengths. In both genotypes, doublet potentiation was greatest at short lengths and decreased as muscle length increased. However, in Ttn ?112-158 muscles, doublet potentiation occurred over a narrow range of lengths and was eliminated on the descending limb of the length-tension relationship. These results are consistent with the hypothesis that PEVK titin contributes to doublet potentiation and that the shorter, stiffer PEVK segment in Ttn ?112-158 muscles increases doublet potentiation but limits the range of lengths over which doublet potentiation takes place.