Figure 3.

Skeletal muscle myosin can play a balancing role involving key blood coagulation reactions. In the left panel, factor Xa and its potent cofactor, factor Va, assemble to form the prothrombinase complex on surfaces such as skeletal muscle myosin (as shown here) or alternatively on the widely recognized procoagulant surface of negatively charged phospholipid membranes (not depicted here). The prothrombinase complex generates thrombin from prothrombin. In the right panel, some of the thrombin formed by the prothrombinase complex binds to thrombomodulin on cell surfaces and generates anticoagulant activated protein C (APC) from protein C. Then, in the presence of myosin, as depicted (or negatively charged phospholipid membranes, not depicted), APC can proteolytically inactivate factor Va, resulting in less thrombin generation. Thus, myosin may not only help to generate thrombin but may also contribute to negative feedback downregulation of excessive thrombin generation. During acute muscle trauma, blood is exposed to myosin and some myosin is released and circulates in plasma. The procoagulant role of skeletal muscle myosin as a membrane substitute could be important in situations such as acute muscle trauma to stop excessive bleeding. The anticoagulant role of skeletal muscle myosin could be important after initial trauma and tissue damage to help reduce excessive generation of thrombin and procoagulant factors.