Cross-bridge Dynamics is Determined by Two Velocity Dependent Kinetics; Implications on the Adaptive and Synchronous Cardiac Function

Introduction: The cardiac muscle has a remarkable ability to adjust function to changes in demands, as described by the Frank-Starling Law, the Fenn effect, and the high contractile efficiency. The loading conditions determine the force per cross-bridge, cross-bridge recruitment and the sarcomeric energy consumption. The length, stress, and velocity of shortening were suggested as possible modulators of cross-bridge dynamics.

Methods: The study tested the effects of the initial length or isometric stress (n=9), and the sarcomere shortening velocity (n=9) on cross-bridge dynamics in the intact rat trabeculae, under constant activation. Sarcomere length was measured by laser diffraction and ramp shortenings at various velocities were imposed with a fast servomotor.

Results: Both stress decline and redevelopment responses revealed two distinct kinetics: a fast and a slower phase. The fast (3 msec) and slow phases depicted linear dependencies of the rate of stress changes on the instantaneous stress levels. The rate coefficients of the two phases were independent of the initial length or stress level. However, they were tightly dependent on the shortening velocity (V_SL). An increase in the V_SL expedited the rates of both phases in a linear mode. The fast kinetics is more than 5 time faster than the slow kinetics, at all velocities. The fast kinetics determines the force per cross-bridge and the second is ascribed to cross-bridge cycling and determines the number of strong cross-bridge.

Conclusion: Cross-bridge dynamics is modulated by the velocity and not by the length or stress. These features shed light on theories of cardiac muscle contraction, and are essential for the regulation and adaptation of cardiac function to match the demands. Shortening velocity synchronizes all the myocytes in the myocardium and therefore its analysis is suggested to assist in optimization of cardiac resynchronization therapies (CRT).