Biophysical Analysis of the Role of the Cross-Bridge Sliding Rate in Modulating Heart Mechanics

초록

We investigated the effects of the cross-bridge sliding rate on heart mechanics from cells to system by using a mathematical model. The alternation of the sliding effect in the cross-bridge filament is mediated through phosphorylation by beta receptor stimulation, which is closely related to heart failure. The formula and related variables were introduced to express the effect of sliding on cellular mechanics. To delineate the sliding effect, we developed a cellular mechanics model that simulated sequential cellular events starting from membrane excitation to contraction. The isotonic simulations with variable loadings showed that the force velocity relation (FVR) was closely related to the cross-bridge sliding rate (CBSR), which quantitatively indicated the sliding effect in cross-bridge dynamics. In the cell system model, computational results showed that the effect of the sliding rate on heart mechanics was mediated by a change in cross-bridge elongation during contraction, which sequentially induced changes in both the cross-bridge-generated force and the systolic pressure of the left ventricle (LV). Therefore, an increased CBSR induced ail increase in the cross-bridge-generated force and the peak LV pressure. It also resulted in upward movement of the FVR curve, indicating that the CBSR could, like noradrenalin, change the heart's contractile state. Simulation results for various preload and afterload changes implied that the afterload-stroke volume (SV) and the Frank-Starling curve of the preload also grew with increasing CBSR.

키워드