Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model

Model Status

This model does not run in OpenCell or COR because all variables are not initialized and some variables are undefined. This is only the case for the component force equations but it seems that all the variables in that component cannot be calculated because some of the equations in the original paper look like partial differential equations which are beyond the scope of CellML.

Model Structure

Abstract: This study describes the regulation of mechanical activity in the intact cardiac muscle, the effects of the free calcium transients and the mechanical constraints, and emphasizes the central role of the troponin complex in regulating muscle activity. A "loose coupling" between calcium binding to troponin and cross-bridge cycling is stipulated, allowing the existence of cross bridges in the strong conformation without having bound calcium on the neighboring troponin. The model includes two feedback mechanisms: 1) a positive feedback, or cooperativity, in which the cycling cross bridges affect the affinity of troponin for calcium, and 2) a negative mechanical feedback, where the filament-sliding velocity affects cross-bridge cycling. The model simulates the reported experimental force-length and force-velocity relationships at different levels of activation. The dependence of the shortening velocity on calcium concentration, sarcomere length, internal load, and rate of cross-bridge cycling is described analytically in agreement with reported data. Furthermore, the model provides an analytic solution for Hill's equation of the force-velocity relationship and for the phenomena of unloaded shortening velocity and force deficit. The model-calculated changes in free calcium in various mechanical conditions are in good agreement with the available experimental results.

The complete original paper reference is cited below:

Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model, A. Landesberg, S. Sideman, 1994, Am. J. Physiol- Heart Circ. Physiol, 267, H779-795. PubMed ID: 8067434