A mathematical model for the isometric contraction of smooth muscle on the basis of the phosphorylated myosin regulation process

Author

Joseph J. Kocinsky, New Jersey Institute of Technology

Document Type

Thesis

Date of Award

5-31-1987

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering Committee

First Advisor

David S. Kristol

Second Advisor

Friedrich PJ Diecke

Third Advisor

Richard Clyde Parker

Abstract

A mathematical model was proposed for the isometric contraction of smooth muscle (i.e., vascular, urterine, & gastrointestinal) that accounts for the experimental observations on tension transients and pCa²⁺-tension curves. The model is based on the elementary reaction kinetics involved in the process; it uses the Ca²⁺-dependent myosin phosphorylation regulatory mechanism in its interpretation. The model is composed of four parts : (a) the activation of myosin light chain kinase; (b) the phosphorylation of myosin light chains; (c) the actin-myosin Mg²⁺ATPase cross-bridge reaction cycle; and (d) the development of isometric tension. The interaction of the four parts leads to the overall mathematical picture on tension development.. In addition to the isometric tension transients and pCa²⁺-tension curves, the model was also able to simulate the following experimental results: the decrease in the affinity of Ca²⁺ for myosin light chain kinase in the presense of Mg²⁺, the decrease in activation due to calmodulin-binding proteins, the relationship between ATP concentration and the pCa²⁺--phosphorylation curves, the calmodulin-dependent shift of Ca²⁺ affinity for phosphorylation, the effect of diffusion rate in isometric contractions, and provide evidence for the ordered phosphorylation mechanism through the isometric tension transients and the pMgATP-tension curves. The model was also able to predict a suitable mechanism for the cross-bridge reaction cycle, the Marston model, through the phosphorylation-tension- stiffness relationship seen in skinned smooth muscle fibers.

Recommended Citation

Kocinsky, Joseph J., "A mathematical model for the isometric contraction of smooth muscle on the basis of the phosphorylated myosin regulation process" (1987). Theses. 3276.
https://digitalcommons.njit.edu/theses/3276