典型文献
Glutamate drives ‘local Ca2+release’ in cardiac pacemaker cells
文献摘要：
The sinoatrial node(SAN)is the origin of the electrical signals for rhythmic heartbeats in mammals.The spontaneous firing of SAN pacemaker cells(SANPCs)triggers cardiac contraction.'Local Ca2+release'(LCR),a unique cellular activity,acts as the'engine'of the spontaneous firing of SANPCs.However,the mechanism of LCR initiation remains unclear.Here,we report that endogenous glutamate drives LCRs in SANPCs.Using a glutamate sensor,we unraveled a tight correlation between glutamate accumulation and LCR occurrence,indicating a potential relationship between glutamate and LCRs.Intracellular application of glutamate significantly enhanced the LCRs in both intact and permeabilized SANPCs.Mechanistically,we revealed that mitochondrial excitatory amino acid transporter 1(EAAT1)-dependent mitochondrial glutamate import promoted ROS generation,which in turn led to the oxidation of Ca2+-handling proteins,ultimately resulting in enhanced LCRs.Importantly,EAAT1 depletion reduced both the spontaneous firing rates of isolated SANPCs and the heart rate in vitro and in vivo,suggesting the central role of EAAT1 as a glutamate transporter in the regulation of cardiac autonomic rhythm.In conclusion,our results indicate that glutamate serves as an LCR igniter in SANPCs,adding a potentially important element to the coupled-clock theory that explains the origin of spontaneous firing.These findings shed new light on the future prevention and treatment of cardiac pacemaker cell-related arrhythmias.
文献关键词：
中图分类号：
作者姓名：
Duanyang Xie;Ke Xiong;Xuling Su;Guanghua Wang;Qicheng Zou;Luxin Wang;Caihong Zhang;Yuting Cao;Beihua Shao;Yixin Zhang;Peidong Zhang;Dandan Liang;Yi Liu;Yi-Han Chen
作者机构：
Department of Cardiology,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,China;Key Laboratory of Arrhythmias of the Ministry of Education of China,Tongji University School of Medicine,Shanghai,China;Institute of Medical Genetics,Tongji University,Shanghai,China;Jinzhou Medical University,Jinzhou,Liaoning,China;Department of Pathology and Pathophysiology,Tongji University School of Medicine,Shanghai,China;Research Units of Origin and Regulation of Heart Rhythm,Chinese Academy of Medical Sciences,Shanghai,China
文献出处：
引用格式：
[1]Duanyang Xie;Ke Xiong;Xuling Su;Guanghua Wang;Qicheng Zou;Luxin Wang;Caihong Zhang;Yuting Cao;Beihua Shao;Yixin Zhang;Peidong Zhang;Dandan Liang;Yi Liu;Yi-Han Chen-.Glutamate drives ‘local Ca2+release’ in cardiac pacemaker cells)[J].细胞研究（英文版）,2022(09):843-854
A类：
sinoatrial,heartbeats,SANPCs,LCRs,permeabilized
B类：
Glutamate,drives,local,Ca2+release,cardiac,pacemaker,cells,node,origin,electrical,signals,rhythmic,mammals,spontaneous,firing,triggers,contraction,Local,unique,activity,acts,engine,However,mechanism,initiation,remains,unclear,Here,report,that,endogenous,glutamate,Using,sensor,unraveled,tight,correlation,between,accumulation,occurrence,indicating,relationship,Intracellular,application,significantly,enhanced,both,intact,Mechanistically,revealed,mitochondrial,excitatory,amino,acid,transporter,EAAT1,dependent,promoted,ROS,generation,which,turn,oxidation,handling,proteins,ultimately,resulting,Importantly,depletion,reduced,rates,isolated,vitro,vivo,suggesting,central,role,regulation,autonomic,conclusion,our,results,indicate,serves,igniter,adding,potentially,important,element,coupled,clock,theory,explains,These,findings,shed,new,light,future,prevention,treatment,related,arrhythmias
AB值：
0.499726
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