Single PASMC model (Gosak et al 2014)

About this model

Original publication:
 Gosak, Marko, et al (2014): "The influence of gap junction network complexity on pulmonary artery smooth muscle reactivity in normoxic and chronically hypoxic conditions." Experimental physiology 99.1 (2014): 272-285.
DOI:10.1113/expphysiol.2013.074971

Model status

The current CellML implementation runs in OpenCOR. The results have been validated against the data extracted from the figures in the published Gosak, Marko, et al (2014). We provide the settings used for the figure reproduction with the simulation results shown under Experiments. The model structure can be found in the documentation of Components. The curation process has been summarized in the Model history and Known issues.

Model overview

This workspace holds a CellML encoding of the Gosak, Marko, et al (2014) model. The Gosak, Marko, et al (2014) model describes major elements involved in transplasmalemmal ion exchange and intracellular Ca2+ handling, while the mathematical formulation was adapted from the Parthimos et al.(1999) and Koenigsberger et al. (2004).

Schematics of the model

A diagrammatic representation of the Gosak, Marko, et al (2014) model.

Modular description

Components

CellML divides the mathematical model into distinct components, which are able to be re-used. The main CellML components are:

  • The major elements involved in transplasmalemmal ion exchange, including:
    • Voltage-operated Ca2 +  channels (VOCC): JVOCCi
    • The plasma membrane Ca2 + -ATPase (PMCA): JPMCAi
    • The Na +  ⁄ Ca2 +  exchanger (NCX): JNCXi
    • The Na +  ⁄ K +  ATPase (NKA): JNKAi
    • Ca2 + - and voltage-operated K +  channels (KC): JKi
    • Cl −  channels (CC): JCli
  • Intracellular Ca2+ handling, including:
    • The sarcoendoplasmic Ca2+-ATPase (SERCA): JSERCAi
    • Calcium Induced Calcium Release (CICR) via the ryanodine receptors: JCICRi
    • Basal Ca2+ leak: Jleaki
  • Ca2 +  concentration in the cytosol (c): Cai

  • Ca2 +  concentration in sarcoplasmic reticulum (s): Casr

  • The dynamics of the cell membrane potential (v): Vm

Each of these blocks is itself a CellML model, which enables us to reuse the various components in future studies and models.

Experiments

Following best practices, this model separates the mathematics from the parameterisation of the model. The mathematical model is imported into a specific parameterised instance in order to perform numerical simulations. The default parameters are defined in Para. The parameterisation would include defining the stimulus protocol to be applied.

This workspace encodes single-cell response to KCl stimulation and corresponding simulation results.

Simulation settings

Simulation settings are encoded in SED-ML files for experiment execution. It is common that we may need to vary experimental settings to obtain data under various conditions. Hence, the full experimental settings are encoded in the simulation scripts. The Python scripts to run simulation and reproduce the figures in the original paper are included under the Simulation/src folder. The runSim.ps1 is used to run the simulation in PowerShell, while plotFig4_0.py, plotFig4_1.py, and plotFig4_ci.py are ready to plot the figures in the single-cell response to KCl stimulation.

Model history

There is no publicly available code for this model.

Known issues

  1. The parameters and initial values listed in Table 1 are not explicitly present in the primary paper. While the model curator used the values from the cited references or assumed some parameters based on the text description, these values may not be the ones that the primary publication used since we could not get confirmation from the original authors.
Parameters
  1. The simulation result is not exactly align with the original data, which could be caused by the parameter settings in Table 1.
Source
Derived from workspace Single PASMC model (Gosak et al 2014) at changeset 309a2cd1708e.
Collaboration
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