Figure 2

Model for cardiac electro-mechanics. Cooperative activation and crossbridge cycling. Model for cardiac electro-mechanics and force generation based on Rice et al. [13] shows states in non-permissive and permissive confirmations of the regulatory proteins. The permissive state transitions into a pre-rotated (XB_PreR) state having a strongly bound crossbridge with the head extended. The transition to the post-rotated (XB_PostR) force-generating state represents the isomerization to induce strain in the extensible neck region. Activation is triggered by the fraction of C a^{2 +} bound troponin regulatory units (T_Reg) which sets the rate constant for transition between the non-permissive (N_XB) to permissive (P_XB) confirmation of the regulatory protein using a strong nonlinearity function to indicate cooperativity. The model assumes that troponin for regulation has affinity set by the thin filament overlap. The affinity for apparent C a^{2 +} binding (used to perturb C a^{2 +} _myo ), not only depends on thin filament overlap but also increases as crossbridges strongly bind to populate the pre-rotated and post-rotated states. The regulatory and apparent C a^{2 +} binding terms are calculated separately to avoid a global feedback from strongly-bound crossbridges to C a^{2 +} binding causing nonphysiological C a^{2 +} sensitivity [13].