Sarcomere Velocity Regulates the Cross-Bridge Cycling Rate in Cardiac Muscle: a Novel Theory for the Muscle Molecular Motor

Abstract

Background: The mechanisms regulating cross-bridges (XBs) cycling during stretch and shortening are controversial. We hypothesize that XB strong to weak transition (weakening) rate increases during shortening and decreases during lengthening in an identical velocity dependent manner. Our hypothesis reproduces the muscle basic properties as the force-velocity relationship and regulation of energy consumption. The study investigates this unifying hypothesis during lengthening and shortening. Methods: Trabeculae were isolated from rat right ventricles (n=9). Sarcomere length was measured by laser diffraction. The number of strong XB (NXB) was evaluated by measuring the dynamic stiffness. Stretches (n=42) and releases (n=48) at different velocities and instants were imposed on sarcomere isometric contractions. Results: Faster stretches yielded larger forces. An overt identical linear correlation between force and NXB development was obtained for any stretch velocity (0-2.17μm/s), implying that the force increased due to the increase in NXB, whereas the unitary force per XB (FXB) was constant. The stiffness development rate linearly depended on the lengthening velocity with a proportion coefficient of 6.9±0.46. Shortening yielded both a decrease in NXB and FXB. Interestingly, the stiffness decline rate depended linearly on the shortening velocity (0-6.27μ/s) with similar proportion coefficient of 6.08±2.45. When identical perturbation (lengthening or shortening) was imposed at different instants during the twitches, similar rate of change in the stiffness and force development were observed. Thus, the phenomena are not dominated by NXB but relate to an inherent property of the single strong XB. Conclusions: The independence of XB weakening rate on the perturbation onset time and the identical dependence on the velocity during shortening and lengthening strongly support the hypothesis that XB dynamics is dominated by a single velocity dependent kinetic.