The ForceLAB simulator: Application to the comparison of current models of cardiomyocyte contraction

Author(s)

da Silva, Robson Rodrigues ^{[1, 2]} ; de Souza Filho, Osias Baptista ^[1] ; Magalhaes Bassani, Jose Wilson ^{[2, 3]} ; Bassani, Rosana Almada ^[2]

Affiliation

^[1] Univ Mogi das Cruzes, Res & Technol Ctr, Mogi Das Cruzes, SP - Brazil

^[2] Univ Estadual Campinas, Ctr Biomed Engn, LabNECC, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Dept Biomed Engn, Sch Elect & Comp Engn, Campinas, SP - Brazil

• Document type: Journal article
• Source: COMPUTERS IN BIOLOGY AND MEDICINE; v. 131, APR 2021.
• Web of Science Citations: 0

Abstract

Mathematical models are useful tools in the study of physiological phenomena. However, due to differences in assumptions and formulations, discrepancy in simulations may occur. Among the models for cardiomyocyte contraction based on Huxley's cross-bridge cycling, those proposed by Negroni and Lascano (NL) and Rice et al. (RWH) are the most frequently used. This study was aimed at developing a computational tool, ForceLAB, which allows implementing different contraction models and modifying several functional parameters. As an application, electrically-stimulated twitches triggered by an equal Ca2+ input and steady-state force x pCa relationship (pCa = -log of the molar free Ca2+ concentration) simulated with the NL and RWH models were compared. The equilibrium Ca2+-troponin C (TnC) dissociation constant (K-d) was modified by changing either the association (k(on)) or the dissociation (k(off)) rate constant. With the NL model, raising K-d by either maneuver decreased monotonically twitch amplitude and duration, as expected. With the RWH model, in contrast, the same K-d variation caused increase or decrease of peak force depending on which rate constant was modified. Additionally, force x pCa curves simulated using Ca2+ binding constants estimated in cardiomyocytes bearing wild-type and mutated TnC were compared to curves previously determined in permeabilized fibers. Mutations increased k(on) and k(off), and decreased K-d. Both models produced curves fairly comparable to the experimental ones, although sensitivity to Ca2+ was greater, especially with RWH model. The NL model reproduced slightly better the qualitative changes associated with the mutations. It is expected that this tool can be useful for teaching and investigation. (AU)

• FAPESP's process: 16/18422-7 - Implementation, evaluation and comparison of contraction force models and / or shortening for rat ventricular myocite
• Grantee: Robson Rodrigues da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/20220-5 - Development and implementation of biophysical models to describe the force of contraction in rat cardiac myocyte REASONED dynamics in calcium
• Grantee: Robson Rodrigues da Silva
• Support Opportunities: Regular Research Grants