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

The optimum length for force generation (L₀) increases as activation is reduced, challenging classic theories of muscle contraction. Although the activation dependence of L₀ is seemingly consistent with length-dependent Ca²⁺ sensitivity, this mechanism cannot explain the apparent force dependence of L₀ or the effect of series compliance on activation-related shifts in L₀. We have tested a theory proposing that the activation dependence of L₀ relates to force depression resulting from shortening against series elasticity. This theory predicts that significant series compliance would cause tetanic L₀ to be shorter than the length corresponding to optimal filament overlap, thereby increasing the activation dependence of L₀. We tested this prediction by determining L₀ and maximum tetanic force (P₀) with (L_{0_spring}, P_{0_spring}) and without added compliance in bullfrog semitendinosus muscles. The activation dependence of L₀ 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 (P_{0_spring} < P₀). We found strong, negative correlations between spring compliance and both P_{0_spring} (r² = 0.89-0.91) and L_{0_spring} (r² = 0.60-0.63; P < 0.001), whereas the activation dependence of L₀ was positively correlated to added compliance (r² = 0.45, P = 0.011). However, since the compliance-mediated reduction in L₀ 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.NEW & NOTEWORTHY Length-dependent Ca²⁺ sensitivity does not fully explain the activation dependence of optimum length (L₀). We demonstrate using an isolated muscle preparation and added series compliance that substantial force depression can arise during an isometric contraction, causing tetanic L₀ 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 L₀.