Antiarrhythmic effects of (-)-epicatechin-3-gallate, a novel sodium channel agonist in cultured neonatal rat ventricular myocytes.
Antiarrhythmic effects of (-)-epicatechin-3-gallate, a novel sodium channel agonist in cultured neonatal rat ventricular myocytes.
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(-)-表儿茶素-3-没食子酸酯（一种新型钠通道激动剂）对培养的新生大鼠心室肌细胞的抗心律失常作用。
DOI：
10.1016/j.bcp.2012.10.003
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发表时间：
2013
影响因子：
5.8
通讯作者：
Lin,Cheng-I
中科院分区：
文献类型：
--
作者：
Wu,AdonisZhi-Yang;Loh,Shih-Hurng;Cheng,Tzu-Hurng;Lu,Hsin-Hsiang;Lin,Cheng-I
（-）-表儿茶素-3-没食子酸酯（ECG）是从绿色茶中提取的多酚，已被提出作为改善心脏收缩力的有效化合物。然而，心电图在治疗心律失常方面的治疗潜力仍然未知。本研究在新生大鼠心室肌细胞（NRVM）原代培养中，观察了ECG对心肌细胞离子电流和兴奋性的直接调节作用，NRVM被认为是分析心肌心律失常的肥大模型。采用全细胞膜片钳技术，发现ECG对电压门控Na+电流的慢失活成分（INa）有浓度依赖性增强作用（0.1-100μM），EC_（50）为3.8μM。ECG不仅使INa峰的电流-电压关系向超极化方向移动，而且使INa恢复动力学加速。在INa增强的浓度水平下，ECG对电压门控性K+电流和L型Ca ~（2+）电流无明显影响。随着培养时间的延长，NRVMs的自发动作电位（sAP）放电频率逐渐降低，培养约1周后出现自发性早期后除极（EAD）。ECG使正常sAP的放电频率增加约2倍，但波形无改变。有趣的是，心动过缓依赖性EAD可以通过快速放电率的ECG显著恢复为正常sAP波形。在整个培养期间，始终检测到优势心脏钠通道亚基Nav1.5的表达。我们的研究结果揭示了ECG，新的INa激动剂，可能作为一个有前途的候选人在心律失常的临床应用。
(−)-Epicatechin-3-gallate (ECG), a polyphenol extracted from green tea, has been proposed as an effective compound for improving cardiac contractility. However, the therapeutic potential of ECG on the treatment of arrhythmia remains unknown. We investigated the direct actions of ECG on the modulation of ion currents and cardiac cell excitability in the primary culture of neonatal rat ventricular myocyte (NRVM), which is considered a hypertrophic model for analysis of myocardial arrhythmias. By using the whole-cell patch-clamp configurations, we found ECG enhanced the slowly inactivating component of voltage-gated Na+currents (INa) in a concentration-dependent manner (0.1–100μM) with an EC50value of 3.8μM. ECG not only shifted the current–voltage relationship of peak INato the hyperpolarizing direction but also accelerated INarecovery kinetics. Working at a concentration level of INaenhancement, ECG has no notable effect on voltage-gated K+currents and L-type Ca2+currents. With culture time increment, the firing rate of spontaneous action potential (sAP) in NRVMs was gradually decreased until spontaneous early after-depolarization (EAD) was observed after about one week culture. ECG increased the firing rate of normal sAP about two-fold without waveform alteration. Interestingly, the bradycardia-dependent EAD could be significantly restored by ECG in fast firing rate to normal sAP waveform. The expression of dominant cardiac sodium channel subunit, Nav1.5, was consistently detected throughout the culture periods. Our results reveal how ECG, the novel INaagonist, may act as a promising candidate in clinical applications on cardiac arrhythmias.