Molecular basis of arrhythmias associated with the cardiac conduction system

The cardiac conduction system is responsible for the initiation and coordination of the heartbeat. It consists of three central components: the sinus node, the atrioventricular node, and the His-Purkinje system. Since the discovery of the sinus node in 1907, the cardiac conduction system has been a topic of immense interest to basic science and clinical researchers investigating the function/dysfunction of the heart. In the last 10 years, our understanding of the system has been immensely enriched. We now know that the system has specialized (different from that in the working myocardium) expression profile of ion channels, intracellular Ca2+-handling proteins, and gap junction channels that are appropriate for its functioning, although there is continued debate concerning the ionic mechanisms underlying pacemaking. We are beginning to understand the mechanisms responsible for cardiac conduction system dysfunction in disease and appreciate how naturally occurring ion channel mutations cause congenital cardiac conduction system dysfunction. In this chapter we present the molecular basis of arrhythmias associated with the cardiac conduction system, with particular emphasis on recent developments in the field.