Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of Polygalae Radix: Suppression of Triggered Activities in Rabbit Myocytes
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概要
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3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) and p-methoxycinnamic acid (PMCA) have been identified as the major bioactive components in the serum collected from rats treated with oral administration of Radix Polygalae (“YuanZhi”, the roots of Polygala tenuifolia Willd), a traditional Chinese medicine used to relieve insomnia, anxiety and heart palpitation. The present study was designed to investigate its direct electrophysiological effects on isolated ventricular myocytes from rabbits. Whole-cell configuration of the patch-clamp technique was used to measure action potential (AP) and membrane currents in single ventricular myocytes enzymatically isolated from adult rabbit hearts. Ca2+ transients were recorded in myocytes loaded with the Ca2+ indicator Fluo-4AM. Among three bioactive substances of Polygala metabolites, only M-TMCA (15∼30 μM) significantly shortened action potential duration at 50% and 90% repolarization (APD50 and APD90) in cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also inhibited L-type calcium current (ICa,L), but showed effect on neither transient outward potassium current (Ito) nor steady-state potassium current (IK,SS). Furthermore, M-TMCA abolished isoprenaline plus BayK8644-induced early afterdepolarizations (EADs) and suppressed delayed afterdepolarizations (DADs) and triggered activities (TAs). This potential anti-arrhythmic effects were likely attributed by the inhibition of ICa,L and the suppression of intracellular Ca2+transients, which consequently suppress the generation of transient inward current (Iti). These findings suggest that M-TMCA may protect the heart from arrhythmias via its inhibitory effect on calcium channel.
著者
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Huang Chen
Department Of General Surgery Affiliated First People's Hospital Shanghai Jiao Tong University
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Zang Wei-jin
Department Of Pharmacology School Of Life Science And Technology Xi'an Jiaotong University
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Xie Lai-Hua
Department of Cell Biology and Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ)
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Huang Chen
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
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Zang Wei-Jin
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
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Zhao Zhenghang
Department of Cell Biology and Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ)
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Fang Minfeng
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University
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Xiao Dandan
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
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Liu Mei
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
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Fefelova Nadezhda
Department of Cell Biology and Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ)
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Liu Mei
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
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Xiao Dandan
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
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