2. Academic Validation
  3. A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles

A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles

  • Cell Res. 2024 Jun 7. doi: 10.1038/s41422-024-00980-x.
Dandan Liang # 1 2 3 4 5,  Liping Zhou # 1 2 3,  Huixing Zhou # 1 2 3,  Fulei Zhang # 1 2 3,  Guojian Fang # 1 2 3,  Junwei Leng 1 2 3,  Yahan Wu 1 2 3,  Yuemei Zhang 1 2 3,  Anqi Yang 1 2 3,  Yi Liu 1 2,  Yi-Han Chen 6 7 8 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 2 Shanghai Arrhythmia Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 3 Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 4 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, China.
  • 5 Clinical Center for Heart Disease Research, Tongji University, Shanghai, China.
  • 6 State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. yihanchen@tongji.edu.cn.
  • 7 Shanghai Arrhythmia Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. yihanchen@tongji.edu.cn.
  • 8 Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. yihanchen@tongji.edu.cn.
  • 9 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, China. yihanchen@tongji.edu.cn.
  • 10 Clinical Center for Heart Disease Research, Tongji University, Shanghai, China. yihanchen@tongji.edu.cn.
  • # Contributed equally.
PMID: 38849501 DOI: 10.1038/s41422-024-00980-x
Abstract

Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic Enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN's protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.

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