Demir, Clark, Giles, 1999

Model Status

This model has been validated by Penny Noble of Oxford University and is known to run in COR and PCEnv to reproduce the published results. A PCEnv session file is also associated with this version.

ValidateCellML verifies this model as valid CellMl but detects unit inconsistencies.

Model Structure

In 1994 S.S. Demir et al published a mathematical modelwhich describes the electrophysiological responses of a rabbit sinoatrial node cell. The model is based on voltage-clamp data from single, isolated myocytes. Ion channels, pumps and exchangers in the sarcolemma are described using equations for these known currents in mammalian pacemaker cells. The extracellular environment is treated as a diffusion limited space, and the myoplasm contains calcium binding proteins (calmodulin and troponin).

In 1999 S.S. Demir et al extended their model of the single rabbit SAN cell to enable it to simulate cellular responses to acetylcholine (ACh) and isoprenaline (Iso) and to mimic the effects of the second-messenger cAMP.

Several lines of evidence suggest that at least three distinct types of ACh-sensitive pathways are capable of modulating the electrical activity of the SAN sarcolemma; the indirect inhibitory affect of ACH via the cAMP mediated pathway which affects the I_f, I_NaK, I_Ca,L and I_K, the G-protein-mediated, direct affect of ACh on I_K,ACh via the extrajunctional M₂/K_ACh muscarinic receptor, and the neuromuscular junction (J type) pathway which affects I_Na and I_B,Na. The components of this rabbit SAN cell model are shown in the figure below.

The complete original paper reference is cited below:

Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model, Semahat S. Demir, John W. Clark and Wayne R. Giles, 1999, American Journal of Physiology , 276, H2221-H2244. PubMed ID: 10362707

A schematic diagram describing the current flows across the cell membrane that are captured in the Demir et al 1999 model of the electrophysiological activity in a SAN cell.

The network defined in the CellML description of the Demir et al 1999 model. For simplicity, not all the variables are shown.