Matsuoka, Sarai, Kuratomi, Ono, Noma, 2003

Model Status

This model has been curated and unit checked by Alan Garny in collaboration with the model authors and it is known to run in COR to reproduce the published results. It also works in JSim as long as the stimulus protocol is altered.

Model Structure

Different types of ion channel, with their distinct gating and conductance properties, play a unique role in generating membrane excitation. Although the behaviours of single ion channels have been extensively studied experimentally, ionic current interactions make it difficult to deduce their individual roles in membrane excitability. In order to better understand the roles of the individual ion currents, Satoshi Matsuoka et al. have developed a mathematical model of membrane excitation for the ventricular cell.

The Matsuoka et al. mathematical model is a development of previously published cardiac cellular models. The group's general approach to modelling was based on the methods used in the Difrancesco-Noble, 1985 Model and the Luo-Rudy Ventricular Model II (dynamic), 1994. In addition, the compound Kyoto Model of Matsuoka et al. incorporates the Negroni and Lascano (1996) model of cardiac muscle contraction, allowing simulation of sarcomere shortening, and also, the gating model of Shirokov et al. is used for both the fast Na⁺ and L-type Ca²⁺ channels.

New experimental data are included, such as new kinetics of the inward rectifier K⁺ channel, the delayed rectifier K⁺ channel, and the sustained inward current (for more details on the reaction kinetics, see figure 3 below). Model simulations showed that ion conductance by the L-type Ca²⁺ channel (I_CaL) dominates the membrane conductance during the action potential. Repolarisation occurs as the following currents are sequentially activated: I_Ks; I_Kr; and I_K1. Agreement between model simulation results and experimental data was taken as supporting evidence for the validity of the model.

The complete original paper reference is cited below:

Role of Individual Ionic Current Systems in Ventricular Cells Hypothesized by a Model Study, Matsuoka S, Sarai N, Kuratomi S, Ono K, and Noma A, 2003, The Japanese Journal of Physiology, 53, 105-123. PubMed ID: 12877767

A schematic diagram describing the ionic components of the Matsuoka et al. 2003 ventricular cell mathematical model. Ions are exchanged between the intracellular and extracellular environments, and between the cytosol and the sarcoplasmic reticulum (SR) via channels and pumps. Unique to the ventricular cells are the transient outward current, I_to, and the slow component of the delayed rectifier K⁺ current, I_Ks.

A schematic diagram describing the reaction kinetics of the ion channel gates in the Matsuoka et al. 2003 mathematical models. A) The kinetics of the sodium channel voltage-dependent gate. B) The kinetics of the Na-Ca exchange pump. C) The kinetics of the Na-K pump. D) The kinetics of the inward rectifier K⁺ current. E) The kinetics of the Ca²⁺-dependent gate of the L-type Ca²⁺ channel. F) The kinetics of the ultra-slow gates of several ion channels. G) The kinetics of the SR Ca²⁺ pump. H) The kinetics of the hyperpolarisation-activated cation current. I) The kinetics of the RyR channel in the SR.