Mahajan, Karma, Garfinkel, Qu, Weiss, Shiferaw, Sato, Baher, Olcese, Xie, Yang, Chen, Restrepo, 2008

Model Status

This model is known to run in OpenCell and COR to reproduce the output shown in the publication. The units have been checked and they are consistent.

Model Structure

ABSTRACT: 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.

Schematic diagram of the Mahajan et al model, featuring whole-cell model showing basic elements of Ca cycling machinery and membrane ion currents, as well as a seven-state Markovian model of the L-type Ca channel.

The original publication reference is cited below:

A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates, Mahajan A, Shiferaw Y, Sato D, Baher A, Olcese R, Xie LH, Yang MJ, Chen PS, Restrepo JG, Karma A, Garfinkel A, Qu Z, Weiss JN, 2008 Biophysical Journal, 94(2):392-410 PubMed ID: 18160660