Volume 12 Issue 7
Jul.  2021
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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. Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons[J]. Protein&Cell, 2021, 12(7): 545-556. doi: 10.1007/s13238-020-00820-9
Citation: 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. Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons[J]. Protein&Cell, 2021, 12(7): 545-556. doi: 10.1007/s13238-020-00820-9

Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

doi: 10.1007/s13238-020-00820-9
Funds:

81770267 and 82070271, to D.L.

This work was funded by the Grants from the National Key Research and Development Plan (2019YFA0801501, to Y.-H.C.

2017YFC1001300, 2016YFC1000208, to Z.X.), Programs of National Natural Science Foundation of China (82088101, 81930013, 81530017 and 81770397, to Y.-H.C.

81900297 and 82070338, to D.X.), Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2017-05), Top-level Clinical Discipline Project of Shanghai Pudong District (PWYgf2018-02), Program for the Research Unit of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences (2019RU045), Innovative research team of highlevel local universities in Shanghai and a key laboratory program of the Education Commission of Shanghai Municipality (ZDSYS14005). Y.- H.C. is a Fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University.

81771651, to Z.X.

  • Received Date: 2020-11-05
  • Rev Recd Date: 2020-12-03
  • Publish Date: 2021-07-08
  • 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 Ca2+ transients frequency in single SANPC. Collectively, 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.
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