A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes.
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.
Luo
C H
CH
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106-7207.
Rudy
Y
Y
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008954:Models, Biological; D015221:Potassium Channels / Q000502:physiology; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase
D015220:Calcium Channels; D002352:Carrier Proteins; D007473:Ion Channels; D015221:Potassium Channels; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium