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Author:

Michael Clerx <michael.clerx@cs.ox.ac.uk>

Date:

2021-05-05 18:05:48+01:00

Desc:

Updates to index.html

Permanent Source URI:

http://models.cellml.org/workspace/5b0/rawfile/5ff25fe53d59b0565bb82ac0748e6d1a659e79b6/index.html

Based on the code for the model by Ni et al. 2017 [1], which is an update of a model by Colman et al. (2013, 2017) [2, 3], which in turn was based on the 1998 model by Courtemanche et al. [4]. The model includes a simplified version of the calcium subspaces used by Koivumaki et al. [5].

The state derivatives from this implementation were verified against output from the original code.

The model contained a mixture of volume and time units (pL, inherited from [5] and um^3, inherited from [4]). This was adjusted so that all rates are in 1/ms and all volumes in um^3. In doing so, a scaling mistake was discovered in the equations for the SR calcium concentrations (

Ca_SR1

and

Ca_SR2

), resulting in the dynamics being sped up. This was not corrected, so that the CellML implementation matches the published code.

The stimulus was set to 0.5ms and -8000pA

[1] Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium Blockers and Acacetin. Ni, Whittaker, Zhang et al. 2017. Frontiers in Physiology https://doi.org/10.3389/fphys.2017.00946

[2] Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria. Colman, Aslanidi, Zhang et al. 2013. Journal of Physiology https://doi.org/10.1113/jphysiol.2013.254987

[3] In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis. Colman, Ni, Zhang, et al. 2017. PLoS Computational Biology https://doi.org/10.1371/journal.pcbi.1005587

[4] Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. Courtemanche, Ramirez, Nattel 1998. American Journal of Physiology https://doi.org/10.1152/ajpheart.1998.275.1.H301

[5] Impact of Sarcoplasmic Reticulum Calcium Release on Calcium Dynamics and Action Potential Morphology in Human Atrial Myocytes: A Computational Study. Koivumaki JT, Korhonen T, Tavi P. 2011. PLoS Comput Biol 7(1): e1001067. https://doi.org/10.1371/journal.pcbi.1001067

Original comments:

Implementation of IKur and INa state-dependent drug blockade. (using guarded-receptor model)

This is the updatd CNZ model, update from the Colman et al. model 2013 Journal of Physiology Paper,

Updates: New IKur Model, Modifications to the conductances of several key ionic currents.

Modifications to the Calcium dynamics model. change in the Refractory Parameters to make it faster, and thus remove the alternans seen at 400 ms of BCL.

RMP: around -76 mV.