Cardiomyopathy-Related Mutations in Cardiac Troponin C, L29Q and G159D, Have Divergent Effects on Rat Cardiac Myofiber Contractile Dynamics

Figure 2

Reduced three-state crossbridge (XB) model scheme depicting regulatory unit (RU; Tm-Tn) kinetics and XB cycling kinetics. This scheme is adapted from Campbell [36]. 𝑘_on and 𝑘_off, represent the RU on/off rates and are functions of Ca²⁺ bound to cTnC. Once turned on by the binding Ca²⁺, RU permits the transition of XB from the non-cycling (𝑁_nc) pool to the cycling pool of XB. The cycling pool of XB includes two states of XB: cycling non-force-bearing (𝑁_𝑐-nfb) and cycling force-bearing (𝑁_𝑐-fb). The transition between non-cycling and cycling pools is mainly regulated by 𝑘_on/𝑘_off kinetics of RU. The influence of the force-bearing XB on the RU on/off kinetics is represented by the feedback arrow (dashed line). 𝑓 and 𝑔 represent the rate constants governing forward transition, 𝑁_𝑐-nfb→𝑁_𝑐-fb, and backward transition, 𝑁_𝑐-fb→𝑁_𝑐-nfb, respectively.