A Spatially Detailed Model of Isometric Contraction Based on Competitive Binding of Troponin I Explains Cooperative Interactions between Tropomyosin and Crossbridges
Fig 1
Each regulatory unit (RU) along the actin-tropomyosin thin filament contains troponin C, which binds calcium, and troponin I, which can bind either to actin or troponin C. These reactions, in addition to the binding of crossbridges, define each of the states. In the schematic, state names with + have calcium bound, state names which include an ‘X’ have crossbridge(s) bound, and B, U, S refer to the labels ‘blocked’, ‘unblocked’, ‘stable unblocked’ at the bottom of the schematic. ‘Blocked’ refers to troponin I bound to actin, which blocks myosin binding. ‘Unblocked’ refers to troponin I being not bound to actin, and ‘stable unblocked’ refers to troponin I being held in place by troponin C. Each state allows for crossbridge binding, although this is very improbable in the ‘blocked’ states, such that states (‘BX’ and ‘BX+’) rarely occur. Note that all transitions between neighbouring states exist, in addition to transitions between the top and bottom rows. The green arrows indicate the main pathway during activation, with Ca2+ binding to TnC, and TnI moving from actin to TnC⋅Ca2+ to allow crossbridge binding. Red arrows indicate the main deactivation pathway, TnI detaching from TnC⋅Ca2+, followd by Ca2+ detaching from TnC and TnI binding to actin to block crossbridge binding.