FCU_EC_coupling.cellml

About this Functional Cell Unit

This model is a Functional Cell Unit of calcium handling within a skeletal muscle cell, leading excitation-contraction coupling.

This is a composite module, composed of several individual modules, and merged together in a modular fashion.

INPUTS:
  • Stimulus current or action potential.
    • Velocity of sarcomere stretching.
OUTPUTS:
  • Tension generated by sarcomere.

Model status

The current CellML implementation compiles in OpenCOR.

Model overview

All components are presented in bond-graph form. Components are made by converting an existing kinetic model and translating into bond-graph form.

Components of the model

Components of the model. The system is divided into four compartments: the cytosol (i), the exterior (o), the sarcoplasmic reticulum (SR) and the diadic space (D). The crossbridge (XB) exists within the cytosol. As indicated in bold, each compartment has its own set of unique ionic species.

A description of the process to find bond-graph parameter is shown in the folder parameter_finder, which relies on the:

  1. stoichiometry of system
  2. kinetic constants for forward/reverse reactions
  • If not already, all reactions are made reversible by assigning a small value to the reverse direction.
  1. linear algebra script, which outputs the bond-graph parameters K and κ.

Here, this solve process is performed in Python.

Modular description

Components

CellML supports importing individual modular components which comprise the FCU. These modules are then able to be re-used in other composite models. These CellML components listed below:

Model components of this FCU, including the source of kinetic origin
Component Abbreviation Source
Calcium leak Ca_leak Luo and Rudy (1994)
Crossbridge Troponin-C XB and TRPN-Ca Niederer et al. (2006) , Land et. al. (2017)
Diadic calcium diffusion DiadCaDiffusion Greenstein and Winslow (2002)
L-type calcium channel LCC Luo and Rudy (1994)
Sodium-calcium exchanger NCX Luo and Rudy (1994)
Sarcolemmal calcium pump pCa Clancy and Rudy (2001)
Phospholamban regulation PLB Saucerman et al. (2003)
Ryanodine receptor RyR Stern et al. (1999)
Sarcoplasmic/endoplasmic Ca2+ ATPase SERCA Tran et al. (2009)

Each of these blocks is itself a CellML model, complete with bond-graph parameters appropriate for the isolated system.