BG_GPCR_B1AR_reduced

About this model

This is a bond-graph model of the metabolism of the G-protein coupled receptor (beta-1 adrenergic receptor, R) and the associated Gs protein in the cardiac cell.

INPUTS:

• Ligand (L) stimulus e.g. isoproterenol

OUTPUTS:

• Change in molar amount of Gsα_GTP

REACTIONS:

• R_switch: Spontaneous activation of R from an inactivate state to a state that can bind a Gs protein
• LR_switch: Similar to R_switch, but with substrate of inactive complex LR
• R_L: the binding of L to R
• R_C: the binding of Gs to R
• R_R: the binding of Gs to complex LR
• Act1: Bundled reactions representing the transient exchange of GDP for GTP on the active RG complex, which forms Gsα_GTP, Gsβγ, GDP and R_tag. The latter is the R protein tagged for internalisation
• Act2: Similar to Act1, but with substrate LRG and product LR_tag
• Hyd: Hydration of GTP on Gsα _GTP, forming Gsα_GDP and phosphate
• Reassoc: Binding of Gsα_GDP and Gsβγ to reform Gs
• Intern_R: Internalisation of R_tag by the GRK and arrestin proteins
• Intern_LR: Similar to Intern_R, but for substrate LR _tag

Model status

The current CellML implementation runs in OpenCOR.

Model overview

This model is based on existing kinetic model, where the mathematics are translated into the bond-graph formalism. This describes the model in energetic terms and forces adherence to the laws of thermodynamics.

For the following figures, all enzymes are shown in maroon.

Fig. 1. Bond-graph formulation of the GPCR-β1AR network

For the above bond-graphs, a '0' node refers to a junction where all chemical potentials are the same. A '1' node refers to all fluxes being the same going in and out of the junction.

Original kinetic model

Saucerman et al: Modeling beta-adrenergic control of cardiac myocyte contractility in silico.

Additional detail on receptor internalisation were provided by Stephen Duffull et al. (University of Otago).