氯化铯增加人诱导多能干细胞来源心肌细胞自发动作电位的节律性  

Cesium chloride increases the rhythmicity of spontaneous action potentials of human induced pluripotent stem cell-derived cardiomyocytes

作　　者：杨礼 宫艺其 吴蕾 张侃[3] 付炜[2] 王伟[2] 郑吉建[3] 朱明[3] Yang Li;Gong Yiqi;WuLei;Zhang Kan;Fu Wei;Wang Wei;Zheng Jijian;Zhu Ming(Department of Anesthesiology,Cancer Hospital Affiliated to Fudan University,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai,200032,P.R.China;Department of Cardiothoracic Surgery,Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University,Shanghai,200127,P.R.China;Department of Anesthesiology,Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University,Shanghai,200127,P.R.China)

机构地区：[1]复旦大学附属肿瘤医院麻醉科,复旦大学上海医学院肿瘤学系,上海200032 [2]上海交通大学附属上海儿童医学中心心胸外科,上海200127 [3]上海交通大学附属上海儿童医学中心麻醉科,上海200127

出　　处：《老年医学与保健》2020年第5期740-745,共6页Geriatrics & Health Care

摘　　要：目的探讨氯化铯对人诱导多能干细胞来源心肌细胞自发动作电位以及起搏电流的影响。方法利用CHIR99021和IWP-2小分子在体外将人诱导多能干细胞分化为心肌细胞。通过免疫荧光和动作电位测定对转化心肌细胞进行形态学和电生理鉴定。利用膜片钳系统记录氯化铯对培养60 d人诱导多能干细胞来源心肌细胞自发动作电位及起搏电流的影响。结果免疫荧光显示人诱导多能干细胞来源心肌细胞高表达心肌肌钙蛋白T(cardiac troponin T,cTnT)心肌标志物,电生理鉴定提示其具有自发动作电位,2 mM氯化铯增快自发动作电位的频率(P=0.003,n=5)。2 mM氯化铯提高动作电位的静息电位(P<0.001,n=5),提高动作电位的阈电位(P<0.001,n=5),降低动作电位的振幅(P=0.002,n=5),缩短动作电位复极90%(APD90)的时间(P<0.001,n=5)。2 mM氯化铯抑制人诱导多能干细胞来源心肌细胞起搏电流的平台期电流以及尾电流有统计学意义(P<0.05,n=5)。结论氯化铯增加人诱导多能干细胞来源心肌细胞自发动作电位的自发节律性,并抑制其起搏电流。Objective To investigate the effect of CsCl on spontaneous action potential and pacing current of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CM).Methods Human in induced pluripotent stem cells were differentiated into cardiomyocytes in vitro with small molecules of CHIR99021 and IWP-2.Morphological and electrophysiological identification of transformed cardiomyocytes were identified by immunofluorescence and action potential measurement.The effects of CsCl on the spontaneous action potential and pacing current of hiPSC-CM cultured for 60 days were recorded by patch clamp system.Results ofluorescence showed that cardiac troponin T(cTnT)was highly expressed in hiPSC-CM;electrophysiological identification indicated that it had spontaneous action potential.2 mM CsCl increases the frequency of spontaneous action potentials(P=0.003).2 mM CsCl increased the resting potential of action potential(P<0.001),increased the threshold potential of action potential(P<0.001),decreased the amplitude of action potential(P=0.002),and shortened the time of action potential repolarization by 90%(APD90)(P<0.001).2 mM CsCl significantly inhibited the platform current and tail current of the pacing current of hiPSC-CM(P<0.05).Conclusion CsCl increases the spontaneous rhythmicity of spontaneous action potential and inhibits the pacing current of hiPSC-CM.

关 键 词：氯化铯 人诱导多能干细胞来源心肌细胞 动作电位 起搏电流 

分 类 号：R965[医药卫生—药理学]