Excitation-contraction coupling and extracellular calcium transients in rabbit atrium: reconstruction of basic cellular mechanisms

Excitation-contraction coupling and extracellular calcium transients in rabbit atrium: reconstruction of basic cellular mechanisms

Model Status

This model has been curated by Penny Noble of Oxford University and is known to run in PCEnv and COR and reproduce the results published in the paper it is based on.

Model Structure

In 1987, D.W. Hilemann and D. Noble published a mathematical model of the atrial action potential. This built upon the Di Francesco-Noble 1985 model and attempted to correct its main deficiency by considering intracellular calcium buffering. Although their model was directed towards atrial cells, it also provided a basis for modelling ventricular cells in species (rat, mouse) with short ventricular action potentials. This model (see the figure below) addressed a number of important questions concerning calcium balance.

The complete original paper reference is cited below:

Excitation-contraction coupling and extracellular calcium transients in rabbit atrium: reconstruction of the basic cellular mechanisms, Hilemann, D.W. and Noble, D. 1987, Proc. R. Soc. Lond. , B230, 163-205. (The full text of the article is available to members on the JSTOR website.) PubMed ID: 2884668

A schematic diagram describing the current flows across the cell membrane that are captured in the Hilemann-Noble model.
The network defined in the CellML description of the Hilemann-Noble model. A key describing the significance of the shapes of the components and the colours of the connections between them is in the notation guide. For simplicity, not all the variables are shown.

The membrane physically contains the currents, pumps and exchangers as indicated by the blue arrows in . The currents act independently and are not connected to each other. Several of the channels encapsulate and contain further components which represent activation and inactivation gates. The addition of an encapsulation relationship informs modellers and processing software that the gates are important parts of the current model. It also prevents any other components that aren't also encapsulated by the parent component from connecting to its gates, effectively hiding them from the rest of the model.

The breakdown of the model into components and the definition of encapsulation and containment relationships between them is somewhat arbitrary. When considering how a model should be broken into components, modellers are encouraged to consider which parts of a model might be re-used and how the physiological elements of the system being modelled are naturally bounded. Containment relationships should be used to provide simple rendering information for processing software (ideally, this will correspond to the layout of the physical system), and encapsulation should be used to group sets of components into sub-models.