Myofilament Calcium Sensitivity: Role in Regulation of In vivo Cardiac Contraction and Relaxation

Figure 1. A hypothetical force-pCa curve demonstrating left- and right-shift (increased and decreased calcium sensitivity, respectively). Bottom. A biochemical equation showing calcium association rate to TnC (kon) and calcium dissociation rate from TnC (koff). A simple equation showing the relationship between equilibrium dissociation constant (Kd), kon, and koff.

Figure 2. A set of hypothetical twitches generated using a Labview (National Instruments) program demonstrating the possible effects of altered calcium sensitivity on twitch kinetics. If the decrease in calcium sensitivity (increase in Kd) is primarily due to decreased kon, one would observe lower developed force (pink). If the decrease in calcium sensitivity is primarily due to increased koff, one would observe lower developed force and faster relaxation kinetics (gray). If the increase in calcium sensitivity (decrease in Kd) is primarily due to decreased koff, one would observe increased developed force and slower relaxation kinetics (dark blue). If the increase in calcium sensitivity (increase in Kd) is primarily due to increased kon, one would observe increased developed force and faster relaxation compared to the case where koff is decreased (green). Calcium transient (light blue) and original twitch (red) are also included in the figure.

Figure 3. A set of hypothetical twitches generated using a Labview (National Instruments) program with the same Kd demonstrating the effect of modulating kon and koff. When kon and koff are both increased by the same factor to yield the same Kd, the contraction and relaxation kinetics speed up (dark blue) and begins to more closely resemble the kinetics of the calcium transient (light blue). When kon and koff are both decreased by the same factor to yield the same Kd, the muscle cannot relax completely at steady-state and has a lower developed force (gray). The original twitch (red) has the same Kd as the other two tracings (dark blue and gray).