Regulatory roles of MgADP and calcium in tension development of skinned cardiac muscle

We investigated the regulatory roles of MgADP and free Ca²⁺ in isometric tension development in skinned bovine cardiac muscle. We found that, in the relaxed state without free Ca²⁺, MgADP elicited a sigmoidal increase in active tension, as is the case in skeletal muscle (ADP-contraction). The critical MgADP concentration, at which the tension increment became half-maximal, increased in proportion to MgATP concentration, with a slope of approximately 1 for cardiac and 4 for skeletal muscle. Raising the free Ca²⁺ concentration decreased the critical MgADP concentration in proportion to the free Ca²⁺ concentration. In addition, the apparent Ca²⁺ sensitivity of tension development increased with MgADP, while decreasing with inorganic phosphate (Pi); MgADP suppressed the Ca²⁺-desensitizing effect of Pi in a concentration-dependent manner. These activating effects of MgADP were quantitatively assessed by means of a model based upon the kinetic scheme of actomyosin ATPase. These experimental results and model simulation suggest that the state of thin filaments is synergistically regulated by both the binding of Ca²⁺ to troponin and the formation of the actomyosin-ADP complex.