Journal Article

Dbh+ catecholaminergic cardiomyocytes contribute to the structure and function of the cardiac conduction system in murine heart

Chen, Ao, Tu, Shu, An, Yanru, Lei, Ming, Grassam-Rowe, Alexander, He, Yu, Shang, Zhouchun, Liu, Zhu, Smart, Nicola, Chen, Tangting, Ren, Huiying, Sun, Tianyi, Hu, Wei, Guo, Xinyu, Zheng, Yuqing, Liu, Yangyang, Xia, Zhidao, Pu, Zhaoli, Ou, Xianhong, Shou, Weinian, Tan, Xiaoqiu, Zhang, Henggui, Li, Yangpeng, Kou, Kun, Fan, Xuehui, Liu, Ying, Miquerol, Lucile, Ren, Yue

2023

Overview

The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbh gene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function. Catecholaminergic transmitters are critical signalling effectors known to be released by sympathetic nerves and adrenomedullary endocrine cells in response to physiological stress. In this paper, the authors demonstrate a uniquely distributed group of catecholaminergic cardiomyocytes with key regulatory roles in cardiac excitation conduction.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/51 / 14 / 14/19 / 38/39 / 38/70 / 38/91 / 631/443/592 / 631/443/592/2726 / 64 / 692/4019/592 / 9/25 / Animals / Biochemistry, Molecular Biology / Cardiology and cardiovascular system / Cardiomyocytes / Cell fate / Conduction / DBH gene / Dopamine / Dopamine beta-Hydroxylase / Dopamine β-monooxygenase / Electrophysiology / Fate maps / Gene deletion / Gene Expression Profiling / Gene mapping / Genetic analysis / Genomics / Heart / Heart - physiology / Heart Conduction System / Heterogeneity / Human health and pathology / Humanities and Social Sciences / Innervation / Life Sciences / Mammals / Mice / multidisciplinary / Myocytes / Myocytes, Cardiac / Physiology / Science / Science (multidisciplinary) / Spatial analysis / Stress (physiology) / Structure-function relationships / Sympathetic nerves / Transcriptomics / Transmitters