Meeting Abstract

42.1  Saturday, Jan. 5  The role of titin in force enhancement along the length-tension curve. PACE, CM*; MONROY, JA; NISHIKAWA, KC; Northern Arizona University; Northern Arizona University; Northern Arizona University

Force enhancement is when steady state muscle forces are larger after stretch and can result in muscle forces that exceed isometric force at Lo, even on the descending limb. This muscle property is not well explained by the sliding filament theory; however, many studies suggest a role for titin in force enhancement via calcium activation of titin. To study titin's contribution to force enhancement, we used an MDM mouse model in which mutant mice have a deletion in the N2A region of their titin protein and exhibit different active and passive in vitro muscle properties compared to wildtype and heterozygote mice. Using the MDM mouse genotypes, we asked how does force enhancement change along the length tension curve and does it vary among the genotypes? Soleus muscles from the MDM genotypes were activated and then subjected to a 5% stretch using a servomotor force lever. Force enhancement was calculated as the difference between the steady state force after stretch and an isometric contraction performed at the stretched length. These muscle tests were performed from -10%Lo to +25%Lo in 5% increments. For all genotypes, passive tension was high, and force enhancement was low, when the muscle was stretched greater than +15%Lo. Mutant mice had particularly high passive tensions, which made their force enhancement appear quite large. However, once passive tension was accounted for, mutant mice showed less force enhancement than the other genotypes. This suggests that having a normal N2A region of titin increases force enhancement. Ultimately, we can use our empirical data to test computer simulations of how titin contributes to force enhancement. Supported by NSF IOS-1025806.