fig4.py

Rapid delayed rectifier potassium current (I_Kr) model optimization

The voltage dependent activation and inactivation gating variables were modeled here. The single exponential voltage-dependent rate constant model was optimized to fit the voltage dependence of I_Kr inactivation in the ten Tusscher 2004 model. The result of inactivation gating is shown in Fig. 4 A and D. Activation gating model were fit to four different data for multiple labs; Ma et al. (2011), Garg et al. (2018), Bellin et al. (2013) and Es-Salah-Lamoureux et al. (2016). Parameters in Ma et al. (2011), Garg et al. (2018) and Es-Salah-Lamoureux et al. (2016). model, were optimized using the time constant activation of Ma et al. (2011). Time constant activation in Bellin et al. (2013) were used in the model. (Fig. 4 C) I-V curve for I_Kr shows in Fig. 4 B.

Current_Ikr.cellml is the main CellML files which has all the formulation for rapid delayed rectifier potassium current, Its associated Sedml file contains all the simulation settings.

All the CellML files and SED-ML files related to this channel need to be downloaded in a same folder (Current_Ikr, gating_Ikr, parameter_Ikr, parameter, unit) as well as python script (fig4.py). In the python script, required Sedml file (Current_Ikr.sedml) is loaded into the script and by running the code following figure is reproduced. fig4.py is used to generate the simulation and reproduces the graph shown in Figure 5 in the original study. In order to reproduce Figure 5, once all the files are downloaded to the same folder, execute the following script from the command line (command prompt):

cd [PathToThisFile]

[PathToOpenCOR]/pythonshell fig4.py

A, optimized activation with dataset-specific model fits. Different colour represent experimental iPSC-CM data from multiple laboratories. B, I-V curve, C, Time constant of I_Kr activation gate. D, Time constant of I_Kr inactivation gate.