42.3 Saturday, Jan. 5 Residual force enhancement: evidence for Ca2+-activation of titin FUQUA, R.D.*; MONROY, J.A.; NISHIKAWA, K.C.; Northern Arizona University; Northern Arizona University; Northern Arizona University firstname.lastname@example.org
When active muscles are stretched, tension increases and then settles to a steady state that is greater than the isometric force at the stretched length. The mechanism underlying this behavior, termed residual force enhancement (RFE), remains unknown. Previous studies have suggested that titin-based stiffness increases in the presence of Ca2+ and contributes to RFE. We hypothesized that the N2A region of titin binds Ca2+ to increase titin stiffness. To elucidate the role of the N2A region during active stretch, we tested soleus muscles from three genotypes of mdm mice, in which the mutant gene has a deletion in the N2A region. Muscles were actively stretched in two of three solutions, Krebs buffer then BDM, which prevents the formation of strongly-bound crossbridges, or Krebs buffer then dantrolene, which inhibits Ca2+ release. By comparing RFE of muscles in these solutions we isolated the effects of Ca2+ activation. BDM was used to determine if crossbridge interaction plays a role in RFE. Dantrolene was used to determine the roles of other elements in muscle that are also Ca2+-dependent. In all three genotypes there was no difference in RFE following stretch in BDM, suggesting that the observed increase in force is not due to crossbridge interaction. However, both wildtype and heterozygous muscles showed a decrease in RFE following stretch in dantrolene, suggesting that RFE is Ca2+-dependent whereas, mdm mutant muscles were not affected. Data from wildtype and heterozygous mice suggest that RFE is due to a non-crossbridge, Ca2+-dependent mechanism. Data from mdm mutants suggest that this mechanism involves the N2A region of titin. Supported by NSF IOS-1025806.