Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model (Basic Model)
This CellML version of the model has been checked in COR and OpenCell. A stimulus protocol has been added to allow the model to simulate action potentials for 5 seconds. The units are consistent and the model runs to recreate the published results. The parameter 'tissue' has been added to switch between the original (default value 0) and 'tissue' (any other value, for example 1) models.
ABSTRACT: BACKGROUND: Computational biology is a powerful tool for elucidating arrhythmogenic mechanisms at the cellular level, where complex interactions between ionic processes determine behavior. A novel theoretical model of the canine ventricular epicardial action potential and calcium cycling was developed and used to investigate ionic mechanisms underlying Ca2+ transient (CaT) and action potential duration (APD) rate dependence. METHODS AND RESULTS: The Ca2+/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was integrated into the model, which included a novel Ca2+-release formulation, Ca2+ subspace, dynamic chloride handling, and formulations for major ion currents based on canine ventricular data. Decreasing pacing cycle length from 8000 to 300 ms shortened APD primarily because of I(Ca(L)) reduction, with additional contributions from I(to1), I(NaK), and late I(Na). CaT amplitude increased as cycle length decreased from 8000 to 500 ms. This positive rate-dependent property depended on CaMKII activity. CONCLUSIONS: CaMKII is an important determinant of the rate dependence of CaT but not of APD, which depends on ion-channel kinetics. The model of CaMKII regulation may serve as a paradigm for modeling effects of other regulatory pathways on cell function.
|Schematic diagram of the Hund and Rudy 2004 Canine Ventricular Cell Model.|
The original paper reference is cited below:
Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model, Thomas J. Hund and Yoram Rudy, 2004, Circulation, 110, 3168-3174. PubMed ID: 15505083