The effect of sarcomere shortening velocity on force generation, analysis, and verification of models for crossbridge dynamics.

The study tests the hypothesis that the transition rate (G) of the cardiac cross-bridge (XB) from the strong force generating state to the weak state is a linear function of the sarcomere shortening velocity (V(SL)). Force (F) was measured with a strain gauge in six trabeculae from the rat right ventricle in K-H solution [(Ca]0 = 1.5 mM, 25 degrees C). Sarcomere length (SL) was measured with laser diffraction techniques. Twitch F at constant SL and the F response to shortening at constant V(SL) (0-8 microm/s; deltaSL 50-100 nm) were measured at varied times during the twitch. The F response to shortening consisted of an initial fast exponential decline (tau = 2 ms), followed by a slow decrease of F. The instantaneous difference (deltaF) between the isometric F (F(M)) and F during the slow phase depended on the duration of shortening (deltat), the instantaneous F(M) and V(SL). deltaF = G1 x F(M) x deltat x V(SL) x (1 -V(SL)/V(MAX)), where V(MAX) is the unloaded V(SL) and G1 was 6.15+/-2.12 microm(-1) (mean +/- s.d.; n=6). DeltaF/F(M) was independent of the time onset of shortening. The linear interrelation between deltaF and V(SL) is consistent with the suggested feedback, whereby XB kinetics depends on V(SL). This feedback provides a more universal description of the interrelation between shortening and force, as well as the observed linear relation between energy consumption and the mechanical energy output.