Arrhythmogenesis toxicity of aconitine is related to intracellular ca(2+) signals.
Arrhythmogenesis toxicity of aconitine is related to intracellular ca(2+) signals.
复制标题
乌头碱的心律失常毒性与细胞内 ca(2 ) 信号有关。
DOI：
10.7150/ijms.6541
复制
发表时间：
2013
影响因子：
3.6
通讯作者：
Shan HL
中科院分区：
文献类型：
--
作者：
Zhou YH;Piao XM;Liu X;Liang HH;Wang LM;Xiong XH;Wang L;Lu YJ;Shan HL
乌头碱是一种众所周知的致心律失常毒素，通过心脏电压门控Na+通道诱导触发活动。然而，乌头碱对细胞内Ca2+信号的影响以前是未知的。研究乌头碱对大鼠心室肌细胞内Ca2+信号的影响，探讨乌头碱致心律失常毒性的可能机制。通过测量l型Ca2+电流、咖啡因诱导的Ca2+释放和NCX和SERCA2a的表达来评估Ca2+信号。全细胞膜片钳技术记录动作电位和触发活动。在大鼠心室肌细胞中，1µM乌头碱可显著延长动作电位持续时间。在较高浓度（5µM和10µM）下，乌头碱诱导的触发活性和延迟后去极化（8例中有6例）被维拉帕米抑制。乌头碱（1µM）显著提高了ICa-L密度，从12.77±3.12 pA/pF提高到18.98±3.89 pA/pF （n=10, p<0.01）。1 μM乌头碱使活化曲线向负电位偏移，使失活曲线向正电位偏移。10 mM咖啡因诱导的Ca2+释放水平明显升高。乌头碱（1µM）增加NCX的表达，降低SERCA2a的表达。综上所述，乌头碱通过加速ICa-L和改变NCX和SERCA2a的表达来增加细胞质[Ca2+]i。然后，细胞质[Ca2+]i的升高诱导触发活性和延迟后去极化。乌头碱的心律失常毒性与细胞内Ca2+信号有关。
Aconitine is a well-known arrhythmogenic toxin and induces triggered activities through cardiac voltage-gated Na+ channels. However, the effects of aconitine on intracellular Ca2+ signals were previously unknown. We investigated the effects of aconitine on intracellular Ca2+ signals in rat ventricular myocytes and explored the possible mechanism of arrhythmogenic toxicity induced by aconitine. Ca2+ signals were evaluated by measuring L-type Ca2+ currents, caffeine-induced Ca2+ release and the expression of NCX and SERCA2a. Action potential and triggered activities were recorded by whole-cell patch-clamp techniques. In rat ventricular myocytes, the action potential duration was significantly prolonged by 1 µM aconitine. At higher concentrations (5 µM and 10 µM), aconitine induced triggered activities and delayed after-depolarizations (6 of 8 cases), which were inhibited by verapamil. Aconitine (1 µM) significantly increased the ICa-L density from 12.77 ± 3.12 pA/pF to 18.98 ± 3.89 pA/pF (n=10, p<0.01). The activation curve was shifted towards more negative potential, while the inactivation curve was shifted towards more positive potential by 1 μM aconitine. The level of Ca2+ release induced by 10 mM caffeine was markedly increased. Aconitine (1 µM) increased the expression of NCX, while SERCA2a expression was reduced. In conclusion, aconitine increased the cytosolic [Ca2+]i by accelerating ICa-L and changing the expression of NCX and SERCA2a. Then, the elevation of cytosolic [Ca2+]i induced triggered activities and delayed after-depolarizations. Arrhythmogenesis toxicity of aconitine is related to intracellular Ca2+ signals.
登录
查看更多内容
影响因子：
9.2
作者：
Zhou Y;Xu W;Han R;Zhou J;Pan Z;Rong H;Li J;Xu C;Qiao G;Lu Y
通讯作者：
Lu Y
影响因子：
3.8
作者：
HERZOG, W H;FEIBEL, R M;BRYANT, S H
通讯作者：
BRYANT, S H
DOI：
10.1016/j.bbrc.2007.01.082
发表时间：
2007-03-23
影响因子：
3.1
作者：
Fu, Min;Wu, Meng;Wang, Zhao
通讯作者：
Wang, Zhao
影响因子：
5.8
作者：
Fu, Min;Li, Ru-Xin;Wang, Zhao
通讯作者：
Wang, Zhao
影响因子：
0.7
作者：
Moroz, V. M.;Lipnitskii, T. N.
通讯作者：
Lipnitskii, T. N.