Symmetric Modulation of Cross-Bridge Kinetics by Sarcomere Velocity during Shortening and Lengthening in Cardiac Trabeculae; A New Insight on Sarcomere Dynamics

Abstract

There is a controversy whether cross-bridge (XB) dynamics is determined by XB displacement, filaments velocity or the load experienced by each XB. The study tests these three hypotheses at the sarcomere level. Methods: Trabeculae were isolated from rat right ventricles (n=9). Sarcomere length was measured by laser diffraction. Changes in the number of strong XBs (NXB) were evaluated by measuring the dynamic stiffness. Ramp stretches and releases at different velocities and onset times were imposed over isometric sarcomere contractions. Results: Stretches yielded parallel increase in the force and stiffness, at all stretch velocities. The force per XB during stretch was constant, independent of the velocity, and equal to the isometric force per XB. This observation is incongruent with a load dependent kinetics. The instantaneous stiffness during the ramp stretches and releases was normalized by the isometric stiffness. Identical changes in the normalized stiffness were observed when identical ramp perturbations (stretch or release) were imposed at different onset times during the twitches. Thus changes in the normalized NXB are not dominated by XB recruitment processes, although the number of available XBs varies with time during the twitch. The normalized stiffness development rate linearly depended on the lengthening velocity with a slope of 6.73±0.98 [1/μm]. During shortening the normalize stiffness decline rate depended linearly on the shortening velocity with identical slope of 6.70±1.43 [1/μm]. Conclusions: The symmetrical dependence of the normalized stiffness development rate on the velocity and the independence on the perturbation onset time are conveniently explained by the velocity dependent hypothesis in the framework of an integrated sarcomere, where there is a cooperative interaction between the XBs. This mechanism explains the force-velocity relationship and the muscle high contractile efficiency.