The molecular basis of cardiac mechanics: regulation of motor unit recruitment

Calcium binding to the regulatory proteins of the contractile filaments allows cross-bridge recruitment and force generation. The study tests the hypothesis that cross-bridge recruitment is regulated by a positive feedback mechanism whereby the number of force generating crossbridges determines the affinity of the regulatory proteins for calcium. The force response to sarcomere length oscillations was measured at constant free Ca²⁺ concentration, during steady tetanus contraction of isolated rat trabeculae, obtained from rat right ventricles (n=5). Tetanus was achieved by using cyclopiazonic acid (CPA) and 8 Hz stimulation. SL was measured by laser diffraction techniques. The force was measured by silicon strain gauge. Sarcomere oscillations were imposed with a fast servomotor. The force response lagged the sarcomere length oscillations at frequency smaller than 4 Hz (99.3 ± 39.9 msec at 1 Hz). A counter clockwise hysteresis was obtained between the force and the SL. There was no unique force-length relation at constant activation since the force was depended on a short-term history of contraction. The study establishes the existence of a positive feedback that regulates cross-bridge recruitment, cardiac mechanics and energetics: the steep force-length relation and the adaptive control of energy consumption by the prevailing loading conditions.