Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of Polygalae Radix : Suppression of Triggered Activities in Rabbit Myocytes

• Zhao Zhenghang

  Department of Pharmacology, School of Medicine, Xi’an Jiaotong University Department of Cell Biology and Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ)

• Fang Minfeng

  Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University

• Xiao Dandan

  Department of Pharmacology, School of Medicine, Xi’an Jiaotong University

• Liu Mei

  Department of Pharmacology, School of Medicine, Xi’an Jiaotong University

• Fefelova Nadezhda

  Department of Cell Biology and Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ)

• Huang Chen

  Department of Pharmacology, School of Medicine, Xi’an Jiaotong University

• Zang Wei-Jin

  Department of Pharmacology, School of Medicine, Xi’an Jiaotong University

• Xie Lai-Hua

  Department of Cell Biology and Molecular Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ)

書誌事項

タイトル別名

• Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of <i>Polygalae Radix</i>: Suppression of Triggered Activities in Rabbit Myocytes

抄録

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. 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 (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 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.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 36 (2), 238-244, 2013

  公益社団法人 日本薬学会

キーワード

• methyl 3,4,5-trimethoxycinnamate
• L-type calcium current
• cardiomyocyte
• action potential
• Ca²⁺ transient
• Polygalae Radix

詳細情報

• CRID: 1390001204631922688
• NII論文ID: 130002480757
• NII論文ID: 40019558475
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b12-00654
• COI: 1:STN:280:DC%2BC3s7ns1OktQ%3D%3D
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 024220099
• PubMed: 23196428
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I024220099
• Web Site: https://www.jstage.jst.go.jp/article/bpb/36/2/36_b12-00654/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013228935
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可