Cooperativity in Mechano-Calcium Feedbacks in Myocardium. Some Conceptual Discrepancies and Overcoming Inconsistency within the Framework of a Mathematical Model
Mechano-calcium feedbacks that provide a fine tuning of electrical and calcium activation of the heart muscle to mechanical conditions of contractions are an important element of the electromechanical coupling as a key mechanism of autoregulation of the myocardium contractile activity. A lot of experimental and theoretical evidences testify to the cooperative dependence of the calcium-troponin kinetics on the cross-bridge concentration as a principal mechanism underlying the mechano-calcium feedback in the intact myocardium. At the same time, experiments performed using skinned myocardial preparations demonstrated that mechanical conditions significantly affected only calcium sensitivity of the relationship Ca<sup>2+</sup>-force rather than its Hill’s coefficient of cooperativity. These data impel some investigators to doubt contribution of the cooperativity to the mechano-calcium feedbacks. To overcome the arising discrepancies we suggest a follow-on conception of cooperativity revealing the extent of intensity differently in steady state and transitional processes. A suggested conception enables us to reproduce and explain within the framework of a mathematical model both the mechanodependence of calcium activation in the intact myocardium and the results obtained with skinned muscle.