Development of the Cardiac Conduction System

Abstract

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. The distinct components of the cardiac conduction system of the heart are essentially myocardial (Figure 1).1–4 The hypothesis that the conduction system may have a neural crest origin has not been supported by evidence. Retroviral labeled single cardiac cells of the early embryonic chicken heart (HH15-17, ±30 somites) were found to give rise to multicellular clones containing both working myocardium and myocardial cells of the conduction system.5,6 Moreover, in both chicken and mouse, labeled neural crest or proepicardial cells were never traced in the conduction system components, even though their descendants were found in close association with these components.6 Figure 1. Schematic overview of heart development in higher vertebrates. The early heart tube has a primitive phenotype (light purple). Chamber myocardium (gray) expands from the outer curvatures of the primary heart tube, whereas nonchamber myocardium (purple) of the inflow tract …