Southern Center for Biomedical Research and Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian Province 350108, PR China.
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Development. 2019 Jul 25;146(14):dev178145. doi: 10.1242/dev.178145.
The sinoatrial node (SAN), the primary cardiac pacemaker, consists of a head domain and a junction/tail domain that exhibit different functional properties. However, the underlying molecular mechanism defining these two pacemaker domains remains elusive. Nkx2-5 is a key transcription factor essential for the formation of the working myocardium, but it was generally thought to be detrimental to SAN development. However, is expressed in the developing SAN junction, suggesting a role for in SAN junction development and function. In this study, we present unambiguous evidence that SAN junction cells exhibit unique action potential configurations intermediate to those manifested by the SAN head and the surrounding atrial cells, suggesting a specific role for the junction cells in impulse generation and in SAN-atrial exit conduction. Single-cell RNA-seq analyses support this concept. Although inactivation in the SAN junction did not cause a malformed SAN at birth, the mutant mice manifested sinus node dysfunction. Thus, defines a population of pacemaker cells in the transitional zone. Despite being dispensable for SAN morphogenesis during embryogenesis, its deletion hampers atrial activation by the pacemaker.
窦房结（SAN）是心脏的主要起搏点，由头域和结/尾域组成，它们表现出不同的功能特性。然而，定义这两个起搏域的潜在分子机制仍不清楚。Nkx2-5 是形成工作心肌所必需的关键转录因子，但通常认为它对 SAN 发育有害。然而， 在发育中的 SAN 结中表达，提示其在 SAN 结发育和功能中的作用。在这项研究中，我们提供了明确的证据，表明 SAN 结细胞表现出独特的动作电位构型，介于 SAN 头和周围心房细胞表现出的构型之间，提示结细胞在冲动产生和 SAN-心房出口传导中具有特定作用。单细胞 RNA-seq 分析支持这一概念。尽管 SAN 结中的 失活在出生时不会导致畸形的 SAN，但突变小鼠表现出窦房结功能障碍。因此， 定义了过渡区中的起搏细胞群体。尽管在胚胎发生期间 对于 SAN 的形态发生不是必需的，但它的缺失会阻碍起搏引起的心房激活。
