Ramirez, Nattel, Courtemanche, 2000

Model Status

This CellML version of the model has been checked in both PCEnv and COR. A few type errors which were in version one of the model have now been fixed and the model runs in both PCEnv and COR but there are several unit inconsistencies which need to be fixed before the model will run to recreate the published results.

Model Structure

Atrial arrhythmias such as atrial fibrillation represent common clinical problems that remain difficult to treat. Dogs have been used extensively to experimentally study atrial arrhythmias, but up until 2000 there had been no published mathematical models of the canine atrial action potential. To obtain insights into the ionic mechanisms underlying many important properties of the canine atrial action potential, Rafael J. Ramirez, Stanley Nattel and Marc Courtemanche incorporated formulations of K⁺, Na⁺, Ca²⁺ and Cl^- currents based on experimental measurements taken from canine atrial myocytes into a mathematical model of the action potential (see the figure below).

The first mathematical model of the action potential was developed by Hodgkin and Huxley to simulate the electrical behaviour of the squid giant axon (please see the CellML version of The Hodgkin-Huxley Squid Axon Model, 1952). Since then mathematical models of action potentials based on formulations of ionic currents, pumps and exchangers have provided insights into the properties of rabbit sinoatrial node (Demir et al 1994), guinea pig ventricular (Luo-Rudy II, 1994), Purkinje fibre (McAllister-Noble-Tsien, 1975), and canine ventricular action potentials (Winslow et al, 1999). More recently, models of the human atrial action potential have been published (Courtemanche et al, 1998 and >Nygren et al, 1998). However, this is the first model representing the canine atrial action potential Such a model would be useful to help interpret experimental data about atrial arrhythmias in vivo in the dog and to consolidate increasing knowledge regarding canine atrial ionic mechanisms. In their study, Ramirez et al found that their model agreed with experimental measurements and that it gave potential insights into the mechanisms underlying functionally important electrophysiological phenomena in the canine atrium.

The complete original paper reference is cited below:

Mathematical analysis of canine atrial action potentials: rate, regional factors, and electrical remodeling, Rafael J. Ramirez, Stanley Nattel and Marc Courtemanche, 2000, American Journal of Physiology , 279, H1767-H1785. (Full text and PDF versions of the article are available for Journal Members on the AJP website.) PubMed ID: 11009464

A schematic representation of the canine atrial myocyte. Intracellular compartments indicate the intracellular pools of ion species. The ion concentration in each pool is affected by ionic currents, pumps and exchangers. The sarcoplasmic reticulum is divided into two compartments: the Ca2+-release compartment, or junctional sarcoplasmic reticulum (JSR) and the Ca2+-uptake compartment, or network sarcoplasmic reticulum (NSR).