%0 Journal Article
%T 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<br>
%A QingHua Zeng
%A XingTing Li
%A GuoGan Zhong
%A WenJie Zhang
%A ChengWen Sun
%A <br>
%J 中国科学C辑(英文版)
%D 2009
%I Springer
%X 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. Supported by the National Natural Science Foundation of China (Grant No. 200830870910).
%K endothelin-1(ET-1)
%K cardiomyocytes
%K intracellular calcium concentration ([Ca2+]i)
%K L-type Ca2+ channel current (ICaL)
%K Ca2+-induced Ca2+ release (CICR)
%K ETA receptors
%K PKC
%K PKA
%K AT1 receptors<br>
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=180CF3A72E750F3261A8A60EDC957784&aid=AF942117C1F62073AD81EC5D4D453F87&yid=DE12191FBD62783C&vid=286FB2D22CF8D013&iid=E158A972A605785F&sid=5DCBAAB000A70168&eid=0918129209B14F3E&journal_id=1674-7305&journal_name=ScienceChina.Lifesciences&referenced_num=0&reference_num=43