Force development and relaxation in cardiac myofibrils activated by myosin strong-binding to actin

Rationale: Calcium (Ca2+) activation of the thin filament cannot solely explain force regulation in cardiac muscles, including the rates of force development, force responses to mechanical perturbations, and relaxation. Cooperative activation between myosin cross-bridges induced by the strong-binding between myosin·actin·ADP has been suggested to also contribute to thin filament activation and force development. Little is known about ADP-induced activation in striated muscles.;Methods: MgADP-induced activation in myofibrils isolated from cardiac muscles were investigated for their force development, force redevelopment following shortening-stretch protocols, and relaxation, and compared to Ca2+-activated myofibrils.;Results: MgADP-activated myofibrils showed a lower rate of force development and redevelopment than Ca2+-activated myofibrils. Furthermore, MgADP activation decreased the rates of relaxation of myofibrils after full force development.;Conclusions: MgADP-induced activation and cooperativity of cross-bridges partially regulate cardiac muscle contraction, including the rates of force development, rates of force changes in response to length perturbations and the rates of relaxation. Thus, the complex myosin·actin·ADP is important in regulating force production, and may be influential in controlling cardiac muscle performance.;Hypotheses: ADP-induced activation and cooperativity between myosin cross-bridges contributes to cardiac force regulation with Ca 2+.