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Meeting Abstract
20.3 Monday, Jan. 4 Activation changes the length and stiffness of elastic elements in soleus muscles of wild-type mice, but not in titin mutants. MONROY, JA; UYENO, TA; GILMORE, LA; POWERS, KA; NISHIKAWA, KC*; Northern Arizona University; Northern Arizona University; Northern Arizona University; Northern Arizona University; Northern Arizona University Kiisa.Nishikawa@nau.edu
Here, we test the hypothesis that Ca2+-activation of muscle results in binding of titin to the thin filament, reducing its length and increasing its stiffness compared to passive muscle. To test the hypothesis, we used mdm mice, which carry an 83 amino acid deletion in the N2A region of titin. Mdm genotypes differ in both passive and active elasticity of the soleus muscles. Passive tension is greater in homozygous mdm mice than in wild-type mice, and intermediate in heterozygotes. We used load-clamp tests to quantify elastic recoil during rapid unloading. In contrast to passive stiffness, active stiffness in load clamp tests was lower in mdm homozygotes than in wild-type mice. To examine the effect of activation on elastic properties, we compared elastic recoil in active soleus muscle at 30% P0 to that observed in the same muscles passively stretched to a length at which the force was equal to that of the activated muscle. In wild-type mice, activation shortened and stiffened spring elements compared to passively stretched muscle at the same force. In mdm homozygotes, there was no change in spring length or stiffness. Results suggest that an epitope of titin binds to the thin filament upon Ca2+-activation in normal mice and this epitope is deleted in mdm mutants. The hypothesis that titin binds to the thin filament in active muscle also accounts for observations that the shape of the length-tension curve depends upon the level of muscle activation, and that muscle force depends on the phase of stimulation in work-loop experiments. It also provides an elastic mechanism for enhancement of force with stretch and depression of force with shortening.