Mathematical modeling of calcium handling dysfunctions leading to atrial fibrillation

Abstract

The aim of this master s thesis is to study the basic cardiac cellular electrophysiology in order to understand and examine the role of SK3 channels. Among the many channels present in an atrial myocyte, SK3 channels are activated by calcium, providing the circulation of the intracellular calcium. A well established mathematical model, the Grandi model, forms the basis of the simulations presented in this project. First, to study the effect of the SK current, a modification of the atrial myocyte model is done. Secondly, the model is calibrated according to experimental results. Lastly, we study the effect of the SK currents to avoid spontaneous calcium release induced depolarizations. Numerical simulations of the whole-cell atrial myocyte performed in this project confirmed the anti arrhythmic behaviour of the SK current, that counteracts the effect of spontaneous calcium release. This effect is, however, not large and, therefore, does not seem to support the, development of SK channel blockers as a new therapeutic strategy in the treatment of atrial fibrillation, as has been suggested in the literature.