康普瑞丁磷酸二钠对豚鼠心室肌细胞动作电位和hERG通道电流的影响  

Effects of combretastatin A4 phosphate on action potential duration and hERG channel currents of ventricle muscle cell in cavy

作　　者：管晓媛[1] 华潞 孟红旭[3] GUAN Xiao-yuan;HUA Lu;MENG Hong-xu(Oxford International Medical Research Center,NHC Key Laboratory of Clinical Research for Cardiovascular Medications,State Key Laboratory of Cardiovascular Disease,National Clinical Research Center of Cardiovascular Diseases,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing100037,China;Thrombosis and Vascular Medicine Center,Chinese Academy of Medical Sciences,Fuwai Hospital,Beijing 100037,China;Beijing Key Laboratory of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Institute of Basic MedicalSciences of Xiyuan Hospital,Beijing 100091,China)

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心阜外医院国家心血管疾病临床医学研究中心心血管疾病国家重点实验室国家卫生健康委员会心血管药物临床研究重点实验室中国牛津国际医学研究中心,北京100037 [2]中国医学科学院阜外医院血栓性疾病诊治中心,北京100037 [3]中国中医科学院西苑医院基础医学研究所中药药理北京市重点实验室,北京100091

出　　处：《现代药物与临床》2019年第5期1269-1273,共5页Drugs & Clinic

摘　　要：目的研究康普瑞汀磷酸二钠(CA4P)对豚鼠心室肌细胞动作电位间期(APD)和人类ether-a-go-go相关基因(hERG)编码的K^+离子通道的影响,探讨CA4P对心脏毒性作用的体外细胞学机制。方法使用全细胞膜片钳技术记录CA4P10、100μmol/L作用下豚鼠心肌细胞的动作电位,并记录CA4P 3、10、30、100、300μmol/L下对HEK293细胞hERG通道尾电流的抑制率及CA4P 30μmol/L在10、20、30、40、50 mV时对h ERG电流的抑制率。结果 CA4P 10、100μmol/L显著延长动作电位复极50%时程(ADP_(50))和动作电位复极90%时程(ADP_(90))。CA4P可浓度相关性和电压相关性抑制hERG尾电流幅度,半数抑制浓度(IC_(50))为54.9μmol/L,安全边缘范围为30.5～2.8。结论 CA4P可延长动作电位间期及抑制hERG通道电流。Objective To investigate the effects of combretastatin A4 phosphate (CA4P) on action potential duration (APD) and human-ether-a-go-go-related gene (hERG) K^+ channel of ventricle muscle cell in cavy,and to explore in vitro celluar mechanism of CA4P in cardiotoxicity effects.Methods APD of ventricle muscle cell in cavy under the action of CA4P 10 and 100 μmol/L were recorded by the whole cell patch clamp technique.The inhibition ratio of hERG channel tail current under the action of CA4P 3,10,30,100,and 300 μmol/L and the inhibition ratio of hERG channel tail current under the action of CA4P 30 μmol/L in 10,20,30,40,and 50 mV were recorded.Results CA4P 10 and 100 μmol/L significantly prolonged the action potential duration at 50% of repolarization (ADP50) and the action potential duration at 90% of repolarization (ADP90).CA4P induced a concentration- and voltage-dependent inhibition of the current amplitude in the hERG tail current.The half-maximal inhibitory concentration (IC50) was 54.9 μmol/L.The safety margin ratio was 30.5-2.8.Conclusion CA4P can prolong APD and inhibit hERG channel current.

关 键 词：康普瑞汀磷酸二钠 QTC间期 动作电位间期 HERG通道 

分 类 号：R966[医药卫生—药理学]