Mysteries of muscle contraction.

According to the cross-bridge theory, the steady-state isometric force of a muscle is given by the amount of actin-myosin filament overlap. However, it has been known for more than half a century that steady-state forces depend crucially on contractile history. Here, we examine history-dependent steady-state force production in view of the cross-bridge theory, available experimental evidence, and existing explanations for this phenomenon. This is done on various structural levels, ranging from the intact muscle to the myofibrillar and isolated contractile protein level, so that advantages and limitations of the various preparations can be fully exploited and overcome. Based on experimental evidence, we conclude that steady-state force following active muscle stretching is enhanced, and this enhancement has a passive and an active component. The active component is associated with the cross-bridge kinetics, and the passive component is associated with a calcium-dependent increase in titin stiffness.