title: Potential antiarrhythmic effect of methyl 3,4,5-trimethoxycinnamate, a bioactive substance from roots of polygalae radix: suppression of triggered activities in rabbit myocytes.
abstract: 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 Polygalae Radix ("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. Ca(2+) transients were recorded in myocytes loaded with the Ca(2+) 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 (APD(50) and APD(90)) in cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also inhibited L-type calcium current (I(Ca,L)), but showed effect on neither transient outward potassium current (I(to)) nor steady-state potassium current (I(K,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 I(Ca,L) and the suppression of intracellular Ca(2+) transients, which consequently suppress the generation of transient inward current (I(ti)). These findings suggest that M-TMCA may protect the heart from arrhythmias via its inhibitory effect on calcium channel.
authors.affiliation: Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi’an 710061, China. zzh@mail.xjtu.edu.cn
authors.forename: Zhenghang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Minfeng
authors.initials: M
authors.lastname: Fang
authors.forename: Dandan
authors.initials: D
authors.lastname: Xiao
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Fefelova
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
authors.forename: Lai-Hua
authors.initials: LH
authors.lastname: Xie
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018517:Plant Roots; D031801:Polygala; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D002934:Cinnamates; D004365:Drugs, Chinese Herbal; C031619:3,4,5-trimethoxycinnamic acid