Disruption of the intracellular Ca2+ homeostasis in the cardiac excitation-contraction coupling is a crucial mechanism of arrhythmic toxicity in aconitine-induced cardiomyocytes
Disruption of the intracellular Ca2+ homeostasis in the cardiac excitation-contraction coupling is a crucial mechanism of arrhythmic toxicity in aconitine-induced cardiomyocytes
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DOI：
10.1016/j.bbrc.2007.01.082
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发表时间：
2007-03-23
影响因子：
3.1
通讯作者：
Wang, Zhao
中科院分区：
文献类型：
--
作者：
Fu, Min;Wu, Meng;Wang, Zhao
乌头碱是重要中药乌头中的一种有效成分。乌头碱也被认为是一种具有致心律失常作用的剧毒二萜生物碱。在本研究中，我们描述了乌头碱对心律失常细胞毒性的特性，并探讨了乌头碱诱导心肌细胞的可能机制。结果表明，乌头碱可引起细胞内钙离子浓度、自发振荡幅度和自发跳动频率的明显异常。此外，乌头碱诱导的心肌细胞中SR Ca2+释放通道RyR(2)和肌层NCX的mRNA转录水平和蛋白表达均升高。然而，与RyR通道抑制剂钌红（RR）共同处理可以逆转乌头碱诱导的细胞内Ca2+信号异常。这些结果表明，在心脏兴奋-收缩偶联（EC偶联）中，细胞内Ca2+稳态的破坏是乌头碱诱导心肌细胞心律失常的关键机制。此外，某些抑制剂似乎在乌头碱诱导的Ca2+依赖性心律失常的解毒中起重要作用。(c) 2007爱思唯尔公司版权所有。
Aconitine is an effective ingredient in Aconite tuber, an important traditional Chinese medicine. Aconitine is also known to be a highly toxic diterpenoid alkaloid with arrhythmogenic effects. In the present study, we have characterized the properties of arrhythmic cytotoxicity and explored the possible mechanisms of aconitine-induced cardiomyocytes. Results show that aconitine induces significant abnormity in the spontaneous beating rate, amplitude of spontaneous oscillations and the relative intracellular Ca2+ concentration. Also, mRNA transcription levels and protein expressions of SR Ca2+ release channel RyR(2) and sarcolemmal NCX were elevated in aconitine-induced cardiornyocytes. However, co-treatment with ruthenium red (RR), a RyR channel inhibitor, could reverse the aconitine-induced abnormity in intracellular Ca2+ signals. These results demonstrate that disruption of intracellular Ca2+ homeostasis in the cardiac excitation-contraction coupling (EC coupling) is a crucial mechanism of arrhythmic cytotoxicity in aconitine-induced cardiomyocytes. Moreover, certain inhibitors appear to play an important role in the detoxification of aconitine-induced Ca2+-dependent arrhythmias. (c) 2007 Elsevier Inc. All rights reserved.