The force produced by muscles varies with muscle length. Compared to isometric contractions at the same final length, force increases after lengthening, known as force enhancement, and decreases after shortening, known as force depression. The mechanisms of force enhancement remain unexplained by the sliding-filament and cross-bridge theories of muscle contraction. Although cross-bridge mechanisms have been proposed to account for force depression, so too have other mechanisms. In addition to cross bridges, titin has been suggested to contribute to both force enhancement and depression. Although titin is too compliant in passive muscles to contribute to active stiffness, recent evidence suggests that calcium activation increases titin stiffness. To test the hypothesis that titin plays a role in force enhancement and depression, we investigated muscle force in active and passive wild type and mdm soleus muscles after isovelocity stretching and shortening at three activation levels. Muscles from mdm mice (muscular dystrophy with myositis) have a predicted 83 amino acid deletion in the N2A region of titin and show no increase in stiffness when activated. We found that: 1) force enhancement and depression were reduced in mdm soleus compared to wild type muscles; 2) force enhancement increased with the amplitude of stretch across all activation levels in wild type and mdm muscles, while force depression increased with amplitude in wild type but not in mdm muscles; and 3) maximal shortening velocity of wild type and mdm muscles was similar, although active stress was reduced in mdm compared to wild type muscles. The results of this study suggest a role for titin in force enhancement and depression, which contribute importantly to regulation of muscle force during natural movements.
All data reported in the paper are included in this excel file.
The excel file has five sheets: 1) animal data and statistics; 2) force enhancement and depression data and statistics relative to isometric force at final length; force-length data and statistics; Hill equation parameters and statistics; and 5) force enhancement and depression data and statistics relative to passive force after stretch to final length.
Funding provided by: National Science Foundation Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000001 Award Number: IOS-0732949
Funding provided by: National Science Foundation Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000001 Award Number: IOS-1025806
Funding provided by: National Science Foundation Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000001 Award Number: IOS-1456868