Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons.

Dandan Liang; Zhigang Xue; Jinfeng Xue; Duanyang Xie; Ke Xiong; Huixing Zhou; Fulei Zhang; Xuling SU; Guanghua Wang; Qicheng Zou; Yi Liu; Jian Yang; Honghui MA; Luying Peng; Chunyu Zeng; Gang LI; Li Wang; Yi-han Chen

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Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons.

Author: Dandan LIANG ¹ ; Zhigang XUE ² ; Jinfeng XUE ² ; Duanyang XIE ¹ ; Ke XIONG ¹ ; Huixing ZHOU ¹ ; Fulei ZHANG ¹ ; Xuling SU ¹ ; Guanghua WANG ¹ ; Qicheng ZOU ¹ ; Yi LIU ¹ ; Jian YANG ¹ ; Honghui MA ¹ ; Luying PENG ¹ ; Chunyu ZENG ³ ; Gang LI ⁴ ; Li WANG ⁵ ; Yi-Han CHEN ⁶
Author Information

1. Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
2. Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200092, China.
3. Department of Cardiology, Daping Hospital, Chongqing, 400042, China.
4. Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
5. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
6. Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. yihanchen@tongji.edu.cn.
Publication Type:Journal Article
Keywords: electrophysiology; glutamatergic neuron; pacemaker cell; single-cell RNA-seq; sinoatrial node
From: Protein & Cell 2021;12(7):545-556
CountryChina
Language:English
Abstract: Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca