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 can't 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 characterised 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), while 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.