Distinct distributions of myosin motor conformations during contraction of slow and fast skeletal muscle.

Slow skeletal muscles maintain posture and produce graded movement at low metabolic cost. ATP utilization during fixed-end contractions is typically five times slower in slow muscles than in fast muscles from the same species. Mechanical measurements previously suggested that more myosin motors are attached to thin filaments during contraction of slow muscle, which seems incompatible with its high efficiency. We therefore used small-angle X-ray diffraction to provide a structural estimate of the fraction of myosin motors attached to thin filaments in slow muscle. The X-ray signals associated with myosin binding to actin indicate that only ∼10% of myosin motors are actin bound during fixed-end tetani of rat soleus slow muscles, compared with ∼25% in mouse extensor digitorum longus fast muscle. Moreover, X-ray signals associated with the helical organization of OFF myosin motors in the thick filaments show that ∼70% of myosin motors remain in the OFF conformation during tetanic contraction of rat soleus muscle, compared with only 30% in mouse extensor digitorum longus muscle. The much slower force development in soleus muscle also allowed clear separation of early structural changes in thick filaments on activation, some of which are distinct from those reported previously in fast muscles. Moreover, the early structural changes in soleus muscle have about the same amplitude in a twitch and a tetanus, suggesting that they are triggered by thin filament activation rather than thick filament stress and implying a fast signalling pathway between thin and thick filaments. KEY POINTS: The interaction between myosin motors and actin filaments in slow skeletal muscles maintains posture and produces graded movement at low metabolic cost. Mechanical studies have suggested that more myosin motors are attached to actin filaments during isometric contraction of slow than fast muscle, but this seems incompatible with its high efficiency. We used X-ray diffraction to show that there are fewer myosin motors attached to actin in slow muscle than in fast muscle because more motors are sequestered on the myosin filament. The slower force development in slow muscle also allowed us to isolate and characterize fast changes in myosin motor conformation associated with activation of the actin filaments.