A novel computational model of the human ventricular action potential and Ca transient
Geoffrey
Nunns
Bioengineering Institute, University of Auckland
Model Status
This CellML model is part of a CellML 1.1 model, this segment contains all the model equations describing cellular species. It is imported by smaller CellML models which describe different voltage protocols, and does not run as a standalone model. The units are consistent throughout.
Model Structure
ABSTRACT: We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: (1) simulate basic excitation-contraction coupling phenomena; (2) use realistic repolarizing K current densities; (3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of I(to) have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient peak and [Na](i). Interestingly, Na accumulation at fast heart rate is a major determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange currents. We investigated the effects of blocking K currents on APD and repolarization reserve: I(Ks) block does not affect the former and slightly reduces the latter; I(K1) blockade modestly increases APD and more strongly reduces repolarization reserve; I(Kr) blockers significantly prolong APD, an effect exacerbated as pacing frequency is decreased, in good agreement with experimental results in human myocytes. We conclude that this model provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single myocyte level.
The original paper reference is cited below:
A novel computational model of the human ventricular action potential and Ca transient, Eleonora Grandi, Francesco S. Pasqualini, Donald M. Bers, 2010, Journal of Molecular and Cellular Cardiology, volume 48, 112-121. PubMed ID: 19835882
A novel computational model of the human ventricular action potential and Ca transient
Nunns
Geoffrey
Rogan
gnunns1@jhu.edu
The University of Auckland
Auckland Bioengineering Institute
2010-04-01
The Grandi et al. 2010 model of human ventricular action potential and calcium transient
This is the CellML description of Grandi et al.'s mathematical model of the 2010 model of human ventricular action potential and calcium transient in human ventricular myocytes
Geoffrey Nunns
Human
cardiac myocyte
keyword
electrophysiology and signal transduction
cardiac
19835882
Grandi
Eleonora
Pasqualini
Francesco
S
Bers
Donald
M
A novel computational model of the human ventricular action potential and Ca transient
2009-09-30
Journal of Molecular and Cellular Cardiology
48
112
121