The Neglected Internodal Tract-A Cardiac Conduction System Structure Homologous to the Development and Regulation of the Sinoatrial Node.

The existence of internodal tracts (ITs) is controversial. Indeed, ITs in the cardiac conduction system (CCS), connected to the sinoatrial node (SAN), transmit electrical signals quickly to the left atrium and the atrioventricular node (AVN). Interestingly, research has suggested that the ITs and the tail of the SAN may share developmental homology. Additionally, many studies indicate that ITs blockage can lead to atrial conduction block and is associated with atrial fibrillation (AF). However, few studies have been reported on the morphogenesis, development, and function of ITs. Therefore, this paper aims to review the morphogenesis, development, and function of ITs, focusing on the regulatory mechanisms of transcription factors (TFs), such as NK2 homeobox 5 (NKX2.5), SHOX homeobox 2 (SHOX2), hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4), and T-box transcription factor 3 (TBX3) in the development and morphogenesis of ITs. This review also explores the causes of arrhythmias, especially atrial block, in order to provide new insights into the pathogenesis of CCS disorders.