Program
| CTH3b | |
|---|---|
| Sharene Bungay | |
| Memorial University | |
| Title | A 2D Model of Calcium Activation in Cardiac Purkinje Cells to explain the source of lethal arrhythmias in post-MI heart |
| Abstract | Purkinje cells (Pcells) are specialized cardiac cells whose role is to carry electrical signals from the pacemaker nodes to the ventricular myocytes. Thus responsible for the initiation and synchronisation of the cardiac beats, Pcells have been involved recently in the generation of spontaneous action potentials underlying lethal arrhythmias (VTs) in patients with myocardial infarction (MI). Although experimental evidences clearly support the idea that the arrhythmogenic electrical activity originates in abnormal spontaneous oscillations of intracellular Ca2+ concentration, the mechanism of Ca2+ handling in normal Pcells remains still unestablished. A 2-dimensional spatio-temporal mathematical model of calcium dynamics within Purkinje cells is presented. The model includes calcium release, uptake, diffusion functions and integrates various ligand interactions. As an extension of the previous model of Stuyvers et al (Circ. Res.2005), the current simulation algorithm includes in particular three types of recently identified intracellular sites of calcium release in canine and swine Pcells (IP3R, RyR2, and RyR3). The constant synergy between computational and experimental data obtained from fast confocal Ca2+ imaging faithfully support the physiological relevance of the model. The final version of the model represents the starting point for the construction of a 3-dimensional model of calcium activation in Purkinje cells, which we anticipate will be instrumental in the identification of molecular abnormalities responsible for post-MI VTs. |
| Coauthors | Kazi Haq, Bruno Stuyvers |
| Location | Woodward 3 |