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PKA信号通路与ryanodine受体介导的心肌肌浆网钙泄漏关系的研究 预览 被引量:2

Relationship between PKA signaling pathway and sarcoplasmic reticulum calcium leakage mediated by the ryanodine receptor
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摘要 目的:研究β肾上腺素激活的PKA信号通路与成年大鼠心肌细胞RyR2介导的肌浆网Ca^2+泄漏之间的关系,探讨治疗心力衰竭的新方法。方法:NiCl2(5mmol/L)和毒胡萝卜素(TG,100nmol/L)分别阻断成年大鼠心室肌细胞的钠钙交换体和钙泵,胞外灌流异丙肾上腺素(ISO,1μmol/L)。采用激光扫描共聚焦显微镜记录灌流前后细胞内钙火花及[Ca2+]i的变化,并使用Ca^2+通道阻断剂钌红(RR,5μmol/L)对β肾上腺素刺激作用进行逆转,进而阻断RyR2介导的肌浆网内钙泄漏。结果:ISO胞外灌流后,心肌细胞钙火花发生率和[Ca^2+]i与对照组相比明显升高(n=10,P〈0.05);加入RR后,心肌细胞内钙火花发生率与对照组比较显著降低(n=20,P〈0.05),[Ca^2+]i两组没有明显差别(n=20,P〉0.05)。结论:ISO激活PKA信号通路后可诱导心肌细胞RyR2介导的钙泄漏,RR可有效地逆转这种钙泄漏。 Objective:To study the relationship between PKA signaling pathway activated by the β-adrenergic and the ryanodine receptorⅡ(RyR2)mediated calcium leak in the cardiac myocytes of adult rat and explore the new way of treating heart failure.Methods:Using the NiCl2(5 mmol/L)and thapsigargin(TG,100nmol/L)respectively to block the sodium-calcium exchanger(NCX)and SR Ca-ATPase(SERCA2),and then perfusing Isoproterenol(ISO,1 μmol/L)within the extracellular solution to activate the PKA signaling pathway in the cardiac myocytes.Finally we employ the the sarcoplasmic reticulum(SR)Ca ^2+ release inhibitor,ruthenium red(RR,5 μmol/L)to rev2erse the function of the ISO.The calcium sparks and[Ca^ 2+ ]i changes were recorded by the laser scanning confocal microscope imaging system.Results:The incidence of calcium sparks and the[Ca ^2+ ]i after perfusing ISO ignificantly increased compared with that under the control conditions(n=10,P0.05);After perfusing RR,the incidence of calcium sparks significantly decreased compared with that of the condition without perfusing RR,(n=20,P0.05),while the[Ca^ 2+ ]i stopped increasing after perfusing RR and the line of[Ca ^2+ ]i gradually became smooth.Conclusion:PKA signaling pathway activated by ISO could induce the calcium leak through RYR2 located on the SR of myocardial cell,and RR could effectively reverse such calcium leak.
作者 刘关省 沈亚峰 王永亮 胡淑婷 汤莹 杨勇骥 LIU Guan-sheng,SHEN Ya-feng,WANG Yong-liang,HU Shu-ting,TANG Ying,YANG Yong-ji(Biophysics Department,The Second Military Medical University,Shanghai 200433,China)
出处 《电子显微学报》 CAS CSCD 北大核心 2009年第6期 567-572,共6页 Journal of Chinese Electron Microscopy Society
基金 国家自然科学基金资助项目(No.30170253) 国家重点基础研究发展计划(973计划)(No.2006CB503807) 军队医药卫生“十一五”科研项目(No.06MB202)~~
关键词 PKA信号通路 RyR2 ISO RR 钙火花发生率 [CA2+]I PKA signaling pathway RyR2 ISO RR calcium sparks [Ca ^2+ ]i
作者简介 作者简介:刘关省(1983-),男(汉族),硕士. 通讯作者:杨勇骥(1956-),男(汉族),上海人,研究员,博士研究生导师.E-mail:yjyang22@163.com.
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