Int J Med Sci 2013; 10(9):1242-1249. doi:10.7150/ijms.6541 This issue Cite

Research Paper

Arrhythmogenesis Toxicity of Aconitine Is Related to Intracellular Ca2+ Signals

Yu-hong Zhou*, Xian-mei Piao*, Xue Liu, Hai-hai Liang, Lei-min Wang, Xue-hui Xiong, Lu Wang, Yan-jie Lu, Hong-li Shan

Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
* These authors contributed equally to this study.

Citation:
Zhou Yh, Piao Xm, Liu X, Liang Hh, Wang Lm, Xiong Xh, Wang L, Lu Yj, Shan Hl. Arrhythmogenesis Toxicity of Aconitine Is Related to Intracellular Ca2+ Signals. Int J Med Sci 2013; 10(9):1242-1249. doi:10.7150/ijms.6541. https://www.medsci.org/v10p1242.htm
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Abstract

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.

Keywords: Aconitine, arrhythmias, L-type Ca2+ current, caffeine-induced Ca2+ release, NCX, SERCA2a


Citation styles

APA
Zhou, Y.h., Piao, X.m., Liu, X., Liang, H.h., Wang, L.m., Xiong, X.h., Wang, L., Lu, Y.j., Shan, H.l. (2013). Arrhythmogenesis Toxicity of Aconitine Is Related to Intracellular Ca2+ Signals. International Journal of Medical Sciences, 10(9), 1242-1249. https://doi.org/10.7150/ijms.6541.

ACS
Zhou, Y.h.; Piao, X.m.; Liu, X.; Liang, H.h.; Wang, L.m.; Xiong, X.h.; Wang, L.; Lu, Y.j.; Shan, H.l. Arrhythmogenesis Toxicity of Aconitine Is Related to Intracellular Ca2+ Signals. Int. J. Med. Sci. 2013, 10 (9), 1242-1249. DOI: 10.7150/ijms.6541.

NLM
Zhou Yh, Piao Xm, Liu X, Liang Hh, Wang Lm, Xiong Xh, Wang L, Lu Yj, Shan Hl. Arrhythmogenesis Toxicity of Aconitine Is Related to Intracellular Ca2+ Signals. Int J Med Sci 2013; 10(9):1242-1249. doi:10.7150/ijms.6541. https://www.medsci.org/v10p1242.htm

CSE
Zhou Yh, Piao Xm, Liu X, Liang Hh, Wang Lm, Xiong Xh, Wang L, Lu Yj, Shan Hl. 2013. Arrhythmogenesis Toxicity of Aconitine Is Related to Intracellular Ca2+ Signals. Int J Med Sci. 10(9):1242-1249.

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