Development and Function of the Cardiac Conduction System in Health and Disease.

David Park,Glenn Fishman

doi:10.3390/jcdd4020007

David Park, Glenn Fishman

Open Access

https://doi.org/10.3390/jcdd4020007

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Abstract

The generation and propagation of the cardiac impulse is the central function of the cardiac conduction system (CCS). Impulse initiation occurs in nodal tissues that have high levels of automaticity, but slow conduction properties. Rapid impulse propagation is a feature of the ventricular conduction system, which is essential for synchronized contraction of the ventricular chambers. 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. 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. Underlying the functional diversity of the CCS are gene regulatory networks that direct cell fate towards a nodal or a fast conduction gene program. 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.

Highlights

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)
The cardiac impulse slows in the atrioventricular node (AVN), which is the last point of communication between the atria and ventricles, providing adequate time for ventricular filling
Loss of Wnt signaling in mice results in structural abnormalities of the tricuspid valve, right ventricle and loss of AV canal (AVC) myocardium [65], whereas ectopic Wnt signaling expanded the boundaries of the AVC and slow conduction gene programming in mice [65] and fish [66]

Summary

Introduction

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). The cardiac impulse slows in the atrioventricular node (AVN), which is the last point of communication between the atria and ventricles, providing adequate time for ventricular filling. 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 rapidly disseminates throughout the ventricular myocardium using the VCS, referred to as the. The HPS allows for: (1) apex-to-basal ventricular contraction; (2) left and right ventricular synchrony; and (3) intraventricular synchrony. This coordinated electrical activity is highly conserved in all mammalian species and is essential to maintain optimal stroke volume.

Cardiac

The Atrioventricular Canal and Node

The Ventricular Conduction System

Conclusions