A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.
Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.
Mahajan
Aman
A
UCLA Cardiovascular Research Laboratory, Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Shiferaw
Yohannes
Y
Sato
Daisuke
D
Baher
Ali
A
Olcese
Riccardo
R
Xie
Lai-Hua
LH
Yang
Ming-Jim
MJ
Chen
Peng-Sheng
PS
Restrepo
Juan G
JG
Karma
Alain
A
Garfinkel
Alan
A
Qu
Zhilin
Z
Weiss
James N
JN
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004553:Electric Conductivity; D006339:Heart Rate / Q000502:physiology*; D007700:Kinetics; D008390:Markov Chains; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism; D009994:Osmolar Concentration; D011817:Rabbits; D015203:Reproducibility of Results; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D016276:Ventricular Function
D002021:Buffers; D020746:Calcium Channels, L-Type; D002118:Calcium