The atrioventricular (AV) junction forms a constriction called the AV canal (AVC) that maintains the slow conduction phenotype of the linear heart tube, serving as the nascent AVN. Subendocardial trabeculated cardiomyocytes in the ventricles undergo further specification to form the highly specialized VCS, whereas in the atria, the pectinated atrial myocardium maintains the fast conduction phenotype without further specification. Rapid conduction is a hallmark feature of cardiac chamber formation, where pectinated myocardium of the atria and trabeculated myocardium in the ventricles adopt a fast conduction phenotype. At the same time, the atrial and ventricular electrocardiogram signals acquire high frequency waveforms, indicative of rapid conduction. At the onset of looping morphogenesis, the ECG morphology changes to show distinct P waves (represents atrial activation on ECG) and QRS waves (represents HPS-dependent ventricular activation on ECG) that are separated by a PQ or PR interval (represents cumulative measure of atrial, AVN and HPS-dependent ventricular activation time on ECG). Electrocardiographic (ECG) recordings at this stage in developing chicks show a sinusoidal waveform. At this stage, the linear heart tube is composed of primary heart field myocardium and conducts impulses slowly. Heart formation begins as a linear tube that maintains circulation via peristaltic contraction. The formation of the CCS occurs simultaneously with cardiac development ( Figure 2). This coordinated electrical activity is highly conserved in all mammalian species and is essential to maintain optimal stroke volume. The HPS allows for: (1) apex-to-basal ventricular contraction (2) left and right ventricular synchrony and (3) intraventricular synchrony. The VCS includes the His bundle, left and right bundle branches and distal Purkinje fiber network. The impulse accelerates again as it enters the penetrating His bundle, which traverses the central fibrous body crossing the annulus fibrosus that electrically isolates atria from ventricles, and then, rapidly disseminates throughout the ventricular myocardium using the VCS, also referred to as the His-Purkinje system (HPS). The cardiac impulse then slows in the atrioventricular node (AVN), which is the last point of communication between the atria and ventricles, providing adequate time for ventricular filling. Upon exiting the SN, impulses travel rapidly through the atrial myocardium, ensuring synchronous contraction of the atrial chambers. The dominant pacemaker is the sinus node (SN) located at the junction between the superior vena cava and the right atrium (RA). ![]() The CCS is functionally divided into the impulse generating, but slowly conducting nodal cells and the rapidly-conducting ventricular conduction system (VCS) as visualized using various conduction system reporter mice ( Figure 1). In this review, we will discuss our current understanding of the transcriptional networks that dictate the components of the CCS, the growth factor-dependent signaling pathways that orchestrate some of these transcriptional hierarchies and the effect of aberrant transcription factor expression on mammalian conduction disease. Underlying the functional diversity of the CCS are gene regulatory networks that direct cell fate towards a nodal or a fast conduction gene program. ![]() Abnormal impulse initiation or propagation can result in brady- and tachy-arrhythmias, producing an array of symptoms, including syncope, heart failure or sudden cardiac death. When functioning properly, the CCS produces ~2.4 billion heartbeats during a human lifetime and orchestrates the flow of cardiac impulses, designed to maximize cardiac output. Rapid impulse propagation is a feature of the ventricular conduction system, which is essential for synchronized contraction of the ventricular chambers. Impulse initiation occurs in nodal tissues that have high levels of automaticity, but slow conduction properties. The generation and propagation of the cardiac impulse is the central function of the cardiac conduction system (CCS).
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