Potential antiarrhythmic effect of methyl 3,4,5-trimethoxycinnamate, a bioactive substance from roots of polygalae radix: Suppression of triggered activities in rabbit myocytes

Zhenghang Zhao, Minfeng Fang, Dandan Xiao, Mei Liu, Nadezhda Fefelova, Chen Huang, Wei Jin Zang, Lai Hua Xie

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) and p-me-thoxycinnamic 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. 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 I Ca,L and the suppression of intracellular Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)238-244
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume36
Issue number2
DOIs
StatePublished - Feb 2013

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Keywords

  • Action potential
  • Ca transient
  • Cardiomyocyte
  • L-type calcium current
  • Methyl 3,4,5-trimethoxycinnamate
  • Polygalae Radix

Fingerprint

Dive into the research topics of 'Potential antiarrhythmic effect of methyl 3,4,5-trimethoxycinnamate, a bioactive substance from roots of polygalae radix: Suppression of triggered activities in rabbit myocytes'. Together they form a unique fingerprint.

Cite this