Meeting Abstract

28.4  Wednesday, Jan. 5  Ca²⁺-activation of skeletal muscle: Not just the thin filament? MONROY, J.A.*; POWERS, K.L.; GILMORE, L.A.; UYENO, T.A.; NISHIKAWA, K.C.; Northern Arizona University Jenna.Monroy@nau.edu

Titin, the largest known protein, contributes to muscle passive tension but its role in active muscle remains elusive. In this study, we investigated the effect of activation on the elastic properties of soleus muscles in mice. We used mice with the muscular dystrophy with myositis (mdm) mutation, which results in a ~779 bp deletion in the Ttn gene. Mdm genotypes differ in both passive and active muscle elasticity. Passive tension is greater in mdm mice than in wild-type mice, and intermediate in heterozygotes. However, during elastic recoil, mdm mice show reduced active stiffness compared to wild-type mice. This difference in passive and active stiffness led to the hypothesis that Ca²⁺-activation of muscle results in binding of titin to the thin filaments, reducing the length and increasing the stiffness of the titin spring compared to passive muscle. Using load-clamp tests, we examined the effect of activation on the elastic recoil of passive and active muscles from mdm, mdm/+ and wild-type mice. Muscles were either activated to 30% P0 or stretched to a length at which the passive force equaled 30% P0. The load was reduced, and elastic recoil was measured. In wild-type mice, activation shortened and stiffened elastic elements compared to passively stretched muscle. However, in mdm mice, there was no change in spring length or stiffness. These results are consistent with the hypothesis that upon Ca²⁺-activation, an epitope of titin, absent in the mdm mutants, binds to the thin filaments. Thus, it appears that like the thin filaments, titin is activated by calcium influx. This idea has important implications for understanding force enhancement with stretch and force depression with shortening. Supported by NSF-IOS-1025806.