The cardiac Na$^+$/K$^+$ ATPase: An updated, thermodynamically consistent model

TL;DR

This paper presents an updated, thermodynamically consistent model of the cardiac Na+/K+ ATPase, including code and corrections to previous formulations, to improve understanding of cardiac cell energetics.

Contribution

It provides a corrected, thermodynamically consistent model of the Na+/K+ ATPase with reproducible code and a bond graph version for better integration into cardiac models.

Findings

Model accurately fits experimental data on ATPase activity.

Corrects errors in previous formulations for thermodynamic consistency.

Provides code and bond graph for community use.

Abstract

The Na$^+$/K$^+$ ATPase is an essential component of cardiac electrophysiology, maintaining physiological Na$^+$ and K$^+$ concentrations over successive heart beats. Terkildsen et al. (2007) developed a model of the ventricular myocyte Na$^+$/K$^+$ ATPase to study extracellular potassium accumulation during ischaemia, demonstrating the ability to recapitulate a wide range of experimental data, but unfortunately there was no archived code associated with the original manuscript. Here we detail an updated version of the model and provide CellML and MATLAB code to ensure reproducibility and reusability. We note some errors within the original formulation which have been corrected to ensure that the model is thermodynamically consistent, and although this required some reparameterisation, the resulting model still provides a good fit to experimental measurements that demonstrate the dependence of Na$^+$/K$^+$ ATPase pumping rate upon membrane voltage and metabolite concentrations. To demonstrate thermodynamic consistency we also developed a bond graph version of the model. We hope that these models will be useful for community efforts to assemble a whole-cell cardiomyocyte model which facilitates the investigation of cellular energetics.