Stimulating Excitability: Advancing cellular electrophysiology models

Abstract

The heart is a muscle pump which provides the body with blood. The contraction and relaxation of the heart muscle is affected by various electrical ion currents. Disruption of these currents by a genetic disorder, or side-effects of drugs can cause cardiac arrhythmia. Understanding the underlying mechanisms of disturbances in the heart rhythm is important, since many people suffer from (lethal) cardiac arrhythmia. In this PhD thesis, existing and novel chemical compounds or drugs are tested on their effect on proteins that underly the ion currents that are responsible for the relaxation of the heart muscle. Furthermore, mutated proteins are studied that facilitate the transport of ions. Also, existing and novel (computer) models are designed and advanced. These models should ultimately lead to more reliable results, which are obtained more efficiently. Finally, a new educational model with examples is presented, in which students execute the whole process of writing and publishing scientific papers.