Effects of shortening velocity on the stiffness to force ratio during isometric force redevelopment suggest mechanisms of residual force depression

Abstract

Although the phenomenon of residual force depression has been known for decades, the mechanisms remain elusive. In the present study, we investigated mechanisms of residual force depression by measuring the stiffness to force ratio during force redevelopment after shortening at different velocities. The results showed that the slope of the relationship between muscle stiffness and force decreased with decreasing shortening velocity, and the y-intercept increased with decreasing shortening velocity. The differing slopes and y-intercepts indicate that the stiffness to force ratio during isometric force redevelopment depends on the active shortening velocity at a given muscle length and activation level. The greater stiffness to force ratio after active shortening can potentially be explained by weakly-bound cross bridges in the new overlap zone. However, weakly-bound cross bridges are insufficient to explain the reduced slope at the slowest shortening velocity because the reduced velocity should increase the proportion of weakly- to strongly-bound cross bridges, thereby increasing the slope. In addition, if actin distortion caused by active shortening recovers during the force redevelopment period, then the resulting slope should be similar to the non-linear slope of force redevelopment over time. Alternatively, we suggest that a tunable elastic element, such as titin, could potentially explain the results.

Does force depression resulting from shortening against series elasticity contribute to the activation dependence of optimum length?

“…Although our findings are consistent with stress-induced cross-bridge inhibition, the mechanism underpinning shortening-induced force depression has received much debate (Herzog, 1998; Rassier & Herzog, 2004; Holt & Williams, 2018; Nishikawa et al, 2018). Titin, a molecular spring responsible for the majority of passive tension in muscle fibres (Prado et al, 2005; Ottenheijm et al, 2009), has also been implicated (Rode et al, 2009; Nishikawa et al, 2012; Jeong & Nishikawa, 2023). Titin’s inherent stiffness increases upon activation through the binding of calcium (Labeit et al, 2003; DuVall et al, 2013).…”

The effect of muscle ultrastructure on the force, displacement and work capacity of skeletal muscle

“…In vertebrates, this large viscoelastic protein [15,25] spans entire half sarcomeres from the Z-disc to M-line [20] and increases stiffness upon muscle activation both by binding to actin [26], and potentially by being wound onto actin filaments by cross-bridge cycling [25,26]. As a result, titin has been suggested to affect muscle force, work and power particularly when the muscle has previously been actively stretched or shortened [15][16][17][18][19]25,91]. The location and size of titin-like proteins appear to vary considerably across invertebrate muscles [83][84][85][86][87][88][89][90], and unlike in vertebrates, very little is known about their active function with the exception of the highly specialized molluscan twitchin [92].…”