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

作　　者：Dandan Liang Liping Zhou Huixing Zhou Fulei Zhang Guojian Fang Junwei Leng Yahan Wu Yuemei Zhang Anqi Yang Yi Liu Yi-Han Chen 

机构地区：[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

出　　处：《Cell Research》2024年第8期556-571,共16页细胞研究（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(82088101 and 81930013 to Y.-H.C.,82122007 and 82070271 to D.L.);the National Key R&D program of China(2019YFA0801501 to Y.-H.C.);the Key Research Center Construction Project of Shanghai(2022ZZ01008 to Y.-H.C.);the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(22SG19443 to D.L.);the Top-level Clinical Discipline Project of Shanghai Pudong District(PWYgf2021-01);the Shanghai Key Clinical Specialty Project(shslczdzk06202);the Research Unit of Origin and Regulation of Heart Rhythm,Chinese Academy of Medical Sciences(2019RU045);the National Key Clinical Specialty and the Fundamental Research Funds for the Central Universities to Y.-H.C.

摘　　要：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 GABAcontaining 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.

关 键 词：VENTRICLE ENDOGENOUS IMPAIRED 

分 类 号：Q421[生物学—神经生物学]