Examining the Electrical Excitation, Calcium Signaling, and Mechanical Contraction Cycle in a Heart Cell

Abstract

As the leading cause of death in the United States, heart disease has become a principal concern in modern society. Cardiac arrhythmias can be caused by a dysregulation of calcium dynamics in cardiomyocytes. Calcium dysregulation, however, is not yet fully understood and is not easily predicted; this provides motivation for the subsequent research. Excitationcontraction coupling (ECC) is the process through which cardiomyocytes undergo contraction from an action potential. Calcium induced calcium release (CICR) is the mechanism through which electrical excitation is coupled with mechanical contraction through calcium signaling. The study of the interplay between electrical excitation, calcium signaling, and mechanical contraction has the potential to improve our understanding of the regular functioning of the cardiomyocytes and help us understand how any dysregulation can lead to potential cardiac arrhythmias. ECC, of which CICR is an important part, can be modeled using a system of partial differential equations that link the electrical excitation, calcium signaling, and mechanical contraction components of a cardiomyocyte. We extend a previous model [Angeloff et al., Spora, 2016] to implement a seven-variable model that includes for the first time the mechanical component of the ECC. We study how the interaction of electrical and calcium systems can impact the cardiomyocyte's levels of contraction.

Challenges and opportunities for the simulation of calcium waves on modern multi‐core and many‐core parallel computing platforms

“…Thus, this work uses a model with seven variables to represent the excitation‐contraction coupling (ECC) occurring in the cardiomyocyte, in which CICR is the mechanism through which electrical excitation is coupled with mechanical contraction through calcium signaling. The results of the simulations by Deetz et al 10,11 allow us to draw two key conclusions about the extension of the model and its implementation: The model is capable of connecting the voltage to the contraction of the heart cell via the cytosol calcium and the third buffer species, and a stronger coupling strength from voltage to calcium leads to stronger contraction.…”

“…The 2016 paper by Angeloff et al 9 also introduced the formulation of the complete eight variable model for all components in Figure 1 (a), but not all model variables were used in the simulations, and the studies did not incorporate the mechanical system. Work by Deetz et al 10,11 contained the first simulations that include the Mechanical Contraction component in Figure 1 (a) by activating the links 3 and 4 in Figure 1 (a). This is facilitated by adding a buffer species whose concentration can be related to the contraction of the cell.…”

“…Work by Deetz et al 10,11 contained the first simulations that include the mechanical contraction component in Figure 1A by activating the links ➂ and ➃ in Figure 1A. This is facilitated by adding a buffer species whose concentration can be related to the contraction of the cell.…”