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

The optimum length for force generation (<i>L</i>₀) increases as activation is reduced, challenging classic theories of muscle contraction. Although the activation dependence of <i>L</i>₀ is seemingly consistent with length-dependent Ca²⁺ sensitivity, this mechanism cannot explain the apparent force dependence of <i>L</i>₀ or the effect of series compliance on activation-related shifts in <i>L</i>₀. We have tested a theory proposing that the activation dependence of <i>L</i>₀ relates to force depression resulting from shortening against series elasticity. This theory predicts that significant series compliance would cause tetanic <i>L</i>₀ to be shorter than the length corresponding to optimal filament overlap, thereby increasing the activation dependence of <i>L</i>₀. We tested this prediction by determining <i>L</i>₀ and maximum tetanic force (<i>P</i>₀) with (<i>L</i>_{0_spring}, <i>P</i>_{0_spring}) and without added compliance in bullfrog semitendinosus muscles. The activation dependence of <i>L</i>₀ was characterized with the addition of twitch and doublet contractions. Springs attached to muscles gave added fixed-end compliances of 11%-39% and induced force depression for tetanic fixed-end contractions (<i>P</i>_{0_spring} < <i>P</i>₀). We found strong, negative correlations between spring compliance and both <i>P</i>_{0_spring} (<i>r</i>² = 0.89-0.91) and <i>L</i>_{0_spring} (<i>r</i>² = 0.60-0.63; <i>P</i> < 0.001), whereas the activation dependence of <i>L</i>₀ was positively correlated to added compliance (<i>r</i>² = 0.45, <i>P</i> = 0.011). However, since the compliance-mediated reduction in <i>L</i>₀ was modest relative to the activation-related shift reported for the bullfrog plantaris muscle, additional factors must be considered. Our demonstration of force depression under novel conditions adds support to the involvement of a stress-induced inhibition of cross-bridge binding.<b>NEW & NOTEWORTHY</b> Length-dependent Ca²⁺ sensitivity does not fully explain the activation dependence of optimum length (<i>L</i>₀). We demonstrate using an isolated muscle preparation and added series compliance that substantial force depression can arise during an isometric contraction, causing tetanic <i>L</i>₀ to shift to a shorter length. Our findings illustrate that series compliance, via the work and length dependencies of force depression, partially uncouples force generation from myofilament overlap, which ultimately increases the activation (or force) dependence of <i>L</i>₀.