The three-state model of thin filament activation. (A) Top: At subsaturating Ca²⁺ levels, the thin filament primarily occupies the B- and C-states. Middle: Ca²⁺ promotes the increased occupancy of the C- and the O-state. Bottom: Myosin crossbridges promote further displacement of regulatory units into the O-state (or M-state). (B) Top: The cross-sectional view of the thin filament axis shows that the largest contribution to the azimuthal rotation of Tm is from the B- to the C-state transition relative to the C- to the O-state (or M-state) transition. Bottom: Superimposition of the strongly bound myosin conformation with the O-state (or M-state) shows unhindered interaction of myosin with actin by Tm. See text for further discussion.