Development of the cardiac pacemaking and conduction system

Abstract

The heartbeat is initiated and coordinated by a heterogeneous set of tissues, collectively referred to as the pacemaking and conduction system (PCS). While the structural and physiological properties of these specialized tissues has been studied for more than a century, distinct new insights have emerged in recent years. The tools of molecular biology and the lessons of modern embryology are beginning to uncover the mechanisms governing induction, patterning and developmental integration of the PCS. In particular, significant advances have been made in understanding the developmental biology of the fast conduction network in the ventricles – the His‐Purkinje system. Although this progress has largely been made by using animal models such as the chick and mouse, the insights gained may help explain cardiac disease in humans, as well as lead to new treatment strategies. Birth Defects Research (Part C) 69:46–57, 2003. © 2003 Wiley‐Liss, Inc.

Left‐asymmetric expression of Galanin in the linear heart tube of the mouse embryo is independent of the nodal co‐receptor gene cryptic

“…1H and I, respectively). Gal transcription in the embryonic heart thus specifically marked the known cell lineage from the AVC to the major components of the secondary pace maker, AVN and AVR (Rentschler et al, 2001;Gourdie et al, 2003;Christoffels et al, 2004). In addition signals were detected in the pulmonary vein (not shown).…”

“…During looping the sinus venosus (inflow tract) is translocated from its initially bilateral symmetrical and posterior position in the linear heart tube to the right atrium of the four chambered heart. This event is of significance, because this region will form the primary pace maker of the cardiac conduction system (CCS; Gourdie et al, 2003). The CCS comprises three components: the sino-atrial node (SAN; primary pace maker), which initiates the heart beat and controls the rate and rhythm of contractions; the atrioventricular (AV) node and ring (secondary pace maker), which acts as a delay generator; and the His/Purkinje bundles, which propagate the action potential to the ventricles (Gourdie et al, 2003;Christoffels et al, 2004).…”

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

“…The specific characteristics of the AV canal are responsible for the "AV delay", an electrical coupling between the slow and fast-conducting segments. This establishment of a two-speed conducting system at the 25th day of development is a critical feature for the proper functioning of the heart [21] , as it guarantees that the ventricular segment will not contract before the contraction of the upstream portions of the heart ends. In the sinus venosus, HCN4 and Tbx3 expression are progressively restricted to a specific area, the "sinus node primordium" or "primary sinoatrial node" [22] ; the other cells from this structure (right and left sinus horns) eventually lose their spontaneous activity and become working atrial myocytes during the "atrialization process".…”

“…The left and right His branches emerge during the interventricular septation, when the trabecular myocytes penetrate inside the compact components of the septum [27] . With the thickening of the ventricle lateral and ventral walls, the trabecular myocytes develop an additional structure, the subendocardial Purkinje network [21,28] , which notably develops in response to an endothelial paracrine effect during the vascularization of the ventricles.…”

Growing the coronary tree: The quail saga

“…Partial localized defects correlate with persisting trabecular (sinusoidal) myocardium and lead to impaired ventricular contractility or sudden cardiac death (Varnava, 2001). Dissection of the molecular cross-talk between the myocardium and coronary arteries, which might direct the growth of vessels and induce conduction fiber differentiation by the arteries (reviewed in Gourdie et al, 2003), would shed more light on this so far obscure entity. …”