InaMo

InaMo is an understandable modular reimplementation of the one-dimensional model of the rabbit atrioventricular node by Inada et al.[1] in the language Modelica. It aims to facilitate reproduction of both the methods and results of Inada et al. and of our own article[2].

The InaMo project also contains Julia scripts for running simulations and testing models and Python scripts for plotting.

The Inada model

The Inada model was the first detailed electrophysiological model of the AV node. It consists of three types of cells (AN: atrionodal, N: nodal, NH: nodal-his), which are connected to a one-dimensional structure along with sinoatrial and atrial cells by other researchers. This implementation currently only contains the individual cell models and not the whole one-dimensional model of the AV node.

The individual cells consist of the following components:

  • ion channels
    • background channel ($I_b$)
    • L-type calcium channel ($I_{Ca,L}$)
    • rapid delayed rectifier channel ($I_{K,r}$)
    • inward rectifier channel ($I_{K,1}$)
    • sodium channel ($I_{Na}$)
    • transient outward channel ($I_{to}$)
    • hyperpolarization-activated channel ($I_f$)
    • sustained outward channel ($I_{st}$)
    • RyanodineReceptor (only used for Ca2+ concentration)
  • ion pumps
    • sodium calcium exchanger ($I_{NaCa}$)
    • sodium potassium pump ($I_p$)
    • SERCA pump (only used for Ca2+ concentration)
  • compartments containing variable Ca 2+ concentrations
    • cytoplasm ($[Ca^{2+}]_i$)
    • junctional sarcoplasmic reticulum (JSR) ($[Ca^{2+}]_{jsr}$)
    • network sarcoplasmic reticulum (NSR) ($[Ca^{2+}]_{nsr}$)
    • “fuzzy” subspace ($[Ca^{2+}]_{sub}$), which is the “functionally restricted intracellular space accessible to the Na+/Ca2+ exchanger as well as to the L-type Ca2+ channel and the Ca2+-gated Ca2+ channel in the SR”
  • concentrations assumed to be constant
    • extracellular calcium concentration ($[Ca^{2+}]_{o}$)
    • intra- and extracellular sodium concentrations ($[Na^{+}]_{i}$, $[Na^{+}]_{o}$)
    • intra- and extracellular potassium concentrations ($[K^{+}]_{i}$, $[K^{+}]_{o}$)

References

  • 1S. Inada, J. C. Hancox, H. Zhang, and M. R. Boyett, “One-dimensional mathematical model of the atrioventricular node including atrio-nodal, nodal, and nodal-his cells,” Biophys. J., vol. 97, no. 8, pp. 2117–2127, 2009, doi: 10.1016/j.bpj.2009.06.056.
  • 2C. Schölzel, V. Blesius, G. Ernst, A. Goesmann, and A. Dominik, “Countering reproducibility issues in mathematical models with software engineering techniques: A case study using a one-dimensional mathematical model of the atrioventricular node,” unpublished, 2021.