Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

作     者：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 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

作者机构：Department of CardiologyEast HospitalTongji University School of MedicineShanghai 200120China Key Laboratory of Arrhythmias of the Ministry of Education of ChinaTongji University School of MedicineShanghai 200120China Institute of Medical GeneticsTongji UniversityShanghai 200092China Department of Regenerative MedicineTongji University School of MedicineShanghai 200092China Reproductive Medicine CenterTongji HospitalTongji University School of MedicineShanghai 200065China Department of Pathology and PathophysiologyTongji University School of MedicineShanghai 200092China Department of CardiologyDaping HospitalChongqing 400042China Department of NeurologyEast HospitalTongji University School of MedicineShanghai 200120China State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2021年第12卷第7期

页      面：545-556页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：The scRNA-seq data of mouse SANPCs in this study have been deposited in the NCBI Sequence Read Archive(accession number SRP192665) The single-cell expression matrix of primary visual CCs was downloaded from Gene Expression Omnibus as reported(GSE71585) Embryonic SAN and adjacent atrial cell data were obtained from Gene Expression Omnibus(GSE130461) 

主　　题：sinoatrial node pacemaker cell glutamatergic neuron single-cell RNA-seq electrophysiology 

摘      要：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 ***,the cellular nature of SANPCs remains ***,we report that SANPCs exhibit glutamatergic neuron-like *** 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 *** and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system,expressing genes encoding glutamate synthesis pathway(G/s),ionotropic and metabotropic glutamate receptors(Grina,Gria3,Grm1 and Grm5)t and glutamate transporters(Slc17a7).SANPCs highly expressed cell markers of glutamatergic neurons(Snap25 and S/-c17a7)t whereas Gad1,a marker of GABAergic neurons,was *** studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca2+transients frequency in single ***,our work suggests that SANPCs share dominant biological properties with glutamatergic neurons,and the glutamatergic neurotransmitter system may act as an intrinsic regulation module of heart rhythm,which provides a potential intervention target for pacemaker cell-associated arrhythmias.