Calcium kinetic and mechanical regulation of the cardiac muscle

Abstract

A comprehensive dynamic model of the excitation contraction coupling, developed for a single cardiac muscle, is extended to a multi-cell system (duplex). The model defines the mechanical activation level based on calcium kinetics and crossbridge cycling and emphasizes the central role of the troponin regulatory proteins in regulating muscle activity. The intracellular control mechanism includes two feedback loops that affect the affinity of troponin for calcium and the crossbridge cycling. The model is used to simulate the basic mechanical characteristics of the cardiac muscle, i. e. the force-length and the force-velocity relationships, and describes their dependence on the mechanical activation level. The two-cell duplex unit is used to study the influence of inter-cellular interactions and the effect of inhomogeneity on muscle performance, due to non-uniformity in the electrical stimulation or inhomogeneity in calcium kinetics. Better understanding of the performance of the inhomogeneous muscle is obtained due to our ability to describe the control of the activation level in each cell.