A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes.

Abstract

A mathematical model of the cardiac ventricular action potential is presented. In our previous work, the membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ and depend on its concentration. The model presented here for the mammalian ventricular action potential is based mostly on the guinea pig ventricular cell. However, it provides the framework for modeling other types of ventricular cells with appropriate modifications made to account for species differences. The following processes are formulated: Ca2+ current through the L-type channel (ICa), the Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma, the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current. Activation of ICa is an order of magnitude faster than in previous models. Inactivation of ICa depends on both the membrane voltage and [Ca2+]i. SR is divided into two subcompartments, a network SR (NSR) and a junctional SR (JSR). Functionally, Ca2+ enters the NSR and translocates to the JSR following a monoexponential function. Release of Ca2+ occurs at JSR and can be triggered by two different mechanisms, Ca(2+)-induced Ca2+ release and spontaneous release. The model provides the basis for the study of arrhythmogenic activity of the single myocyte including afterdepolarizations and triggered activity. It can simulate cellular responses under different degrees of Ca2+ overload. Such simulations are presented in our accompanying article in this issue of Circulation Research.

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

“…Along with human ventricular models, which are discussed in detail below, ventricular models have been developed for guinea pig (Luo and Rudy 1991, Nordin 1993, Luo and Rudy 1994, Noble et al 1998, Faber and Rudy 2000, canine , Fox et al 2002, Greenstein and Winslow 2002, Cabo and Boyden 2003, Hund and Rudy 2004, Flaim et al 2006, rabbit (Puglisi and Bers 2001, Shannon et al 2004, Mahajan et al 2008, rat (Pandit et al 2001), and mouse (Bondarenko et al 2004, Wang andSobie 2008). The existence of species-specific ventricular models is a significant improvement over earlier, more generic ventricular models and recognises the differences in current contributions across species.…”

Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

“…12 In this model, calcium handling is based on the ventricular model by Luo and Rudy. 44,45 The formulation of Ca 2+ release from the SR reflects the close coupling of L-type Ca 2+ channels and SR Ca 2+ release channels. In addition, the formulation is completely analytic and does not require the identification of some trigger event (see Courtemanche et al 12 for details).…”

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

“…Membrane kinetics were represented by the Luo-Rudy dynamic model (Luo and Rudy, 1994) augmented for defibrillation (Ashihara and Trayanova, 2004). Transmural ventricular heterogeneities in the transient outward potassium current (I to ), in the slow and rapid delayed rectifier potassium currents (I Ks , I Kr ), and in the sodium (I Na ) current were incorporated in the model based on experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Dumaine et al, 1999;, as done previously (Saucerman et al, 2004).…”