Why Are Some Regions of the Heart More Arrhythmogenic Than Others?

The conduction system of the heart initiates and coordinates the electric signal that causes the rhythmic and synchronized contractions of the atria and ventricles. In higher vertebrates, this system comprises the sinuatrial (SAN) and atrioventricular nodes (AVN) and the “wiring” of the ventricles. The latter comprises the atrioventricular bundle (AVB), the left and right bundle branches (BBs), and the peripheral ventricular conduction system (PVCS). Failure in the function of the nodes or bundles leads to arrhythmias, requiring electronic pacemaker implantation. On the other side, ectopic pacemaker or conductive activity may cause arrhythmias requiring intervention. Recent progress in molecular-genetic and developmental biology has lead to novel insights into the processes underlying the formation of the conduction system. These insights provide a framework that helps to understand pathologies of the conduction system. In this review, we focus on the cellular origin of the conduction system components, the molecular-genetic mechanisms that control their differentiation, and their impact on arrhythmias.