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Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes

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Abstract

Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.

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Authors and Affiliations

  1. Laboratory of Molecular & Cellular Physiology, School of Life Sciences, Northeast Normal University, Changchun, 130024, China

    QingHua Zeng & XingTing Li

  2. Department of Physiology, School of Basic Medical Sciences, Jilin University, Changchun, 130021, China

    GuoGan Zhong & WenJie Zhang

  3. Department of Pharmaceutical Sciences, North Dakota State University, Fargo, NorthDakota, USA

    ChengWen Sun

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  1. QingHua Zeng
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Correspondence to QingHua Zeng.

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Supported by the National Natural Science Foundation of China (Grant No. 200830870910).

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Zeng, Q., Li, X., Zhong, G. et al. Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes. SCI CHINA SER C 52, 360–370 (2009). https://doi.org/10.1007/s11427-009-0046-z

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