ForceLAB Simulator Update: A Study on the Positive Cooperativity of Cross-Bridge Formation in Ventricular Myocyte

Cardiovascular diseases are one of the leading causes of death in the world. Understanding the mechanisms that control heart contraction is essential to deal with this problem. As auxiliary tools, mathematical models have been used to describe these phenomena at the cellular level. Electrical and mechanical models of ventricular myocytes have been implemented in computer simulators for analysis. One of them is ForceLAB, in which two of the main models of contraction force were implemented: Rice et al. (1999) (RWH) and Negroni & Lascano (2008) (NL). The objective of this paper is to present an updated version of the ForceLAB tool, to which additional features were added, among which the values of important variables, as one of the outputs. The new version of ForceLAB was implemented using App Designer for the development of the new interfaces. As an application, the influence of the positive crossbridge cooperativity on the unusual behavior of the Ca2+-force relationship simulated with the RWH was tested. The waveforms of twitch transient of cytosolic Ca2+ concentration ([Ca2+]i), developed force and the force versus pCa curve (where pCa = −log [Ca2+]i) were simulated. The simulation results showed that the non-paralel shift of the force versus pCa curve upon variation of myofilament Ca2+ was not corrected by the absence of the positive cooperativity mechanism did in the RWH model formulation.