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

Abstract

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 cant 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 (L0_spring, P0_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 this added compliance induced force depression for tetanic fixed-end contractions (P0_spring/P0 < 1). We found strong, negative correlations between spring compliance and both P0_spring (r2 = 0.89-91) and L0_spring (r2 = 0.60-63; 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.