Bondarenko, Szigeti, Bett, Kim, Rasmusson, 2004

Model Status

This version has been curated by Penny Noble from Oxford University and is known to run in COR and PCEnv. This model represents the APICAL CELL variant as described in Bondarenko et al.'s 2004 paper The model is able to reproduce the action potential traces from Figure 16 of the publication.

ValidateCellML verifies this model as valid CellML, but detects unit inconsistency. COR asserts that the units are consistent.

Model Structure

Mathematical models, which describe cardiac action potentials, have been a valuable tool in enhancing our understanding of the molecular mechanisms which underlie the physiological processes. The earliest cardiac models were based on the pioneering work of Hodgkin and Huxley, who in 1952 published a mathematical model which described the Na+ and K+ currents in the giant squid axon (for more details, please see The Hodgkin-Huxley Squid Axon Model, 1952). Over time, advances in experimental techniques have allowed more detailed physiological data to be produced. In turn this has been used to build more biologically realistic, detailed mathematical models which include more complex ionic currents and fluxes.

A diverse array of models have been developed in order to address the wide range of action potential behaviours observed in different species and regions of the heart. These include:

  • Ventricular Myocytes

  • Atrial Myocytes

  • Purkinje Fibres

  • Pacemaker Cells

  • Rabbit

  • Guinea-pig

  • Bullfrog

  • Human

Variation in the shape and duration of the action potential is often due to differences in species and the region of the heart - as opposed to the size of the heart per se. There is a great diversity in the anatomical and electrophysiological features of myocytes from different species, such as the transverse tubules, Ca2+ handling systems, and the specific properties of the ionic currents.

In the Bondarenko et al. 2004 publication described here, the authors develop a computer model of the mouse ventricular action potential (see the figure below). The model includes parameters for both the apex and the septum regions of the heart (the apex parameters have been substituted into the CellML version of the model described in ), and this helps to illustrate how there are regional differences in myocyte repolarisation in the mouse heart. The model is based on recent experimental data from adult mice experiments. The model contains transmembrane pumps, currents and exchangers, as well as a detailed description of the Ca2+ handling system. Where possible, Markov models (see the figure below) have been used to represent the molecular function and structure of ion channels.

The complete original paper reference is cited below:

A Computer Model of the Action Potential of the Mouse Ventricular Myocytes, Vladimir E. Bondarenko, Gyula P. Szigeti, Glenna C. L. Bett, Song-Jung Kim, and Randall L. Rasmusson, 2004, American Journal of Physiology PubMed ID: 15142845

Schematic diagram of the mouse model ionic currents and calcium fluxes.
State diagram of the Markov model for the sodium channel. CNa denotes a closed channel state, ONa is the open state, IFNa represents the fast, inactivated state, I1Na and I2Na are the intermediate inactivated states, and IC2Na and IC3Na are the closed-inactivation states.