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叶江川,刘班,李俊,等.发动蛋白对心脏收缩-频率反应的调控作用[J].同济大学学报（医学版）,2012,33(4):7-12. [点击复制]
YE Jiang-chuan,LIU Ban,LI Jun,et al.Modulation of cardiac force-frequency response by dynamin[J].同济大学学报（医学版）,2012,33(4):7-12. [点击复制]

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发动蛋白对心脏收缩-频率反应的调控作用
叶江川^1,2,刘班^1,2,李俊^1,2,陈义汉^1,2
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摘要:

目的观察DNM2在心脏收缩-频率反应(force-frequency response,FFR)中的作用。方法分离培养大鼠心脏细胞。构建包含DNM2显性失活突变体的腺病毒载体,将其转染成年大鼠心室肌细胞,并分析DNM2功能失活对心肌细胞FFR的影响。通过免疫印迹方法检测受磷蛋白与钙—钙调素依赖的蛋白激酶Ⅱδ(CaMKⅡδ)的活性变化。用选择性药物抑制DNM2的GTP酶活性,观察离体心脏FFR的变化情况。结果 DNM2显性失活减弱了心肌细胞频率依赖的缩短分数和钙瞬变变化,这与细胞钙水平升高及CaMKⅡδ活性上调有关。器官层面的研究显示,抑制DNM2活性还可导致心脏FFR受到明显的损伤。结论 DNM2活性对心脏正常FFR的维持是必需的;作为调控FFR的重要分子,DNM2可能成为心力衰竭等心脏疾病的药物干预靶点。

关键词: 发动蛋白收缩-频率反应钙水平受磷蛋白钙-钙调素依赖的蛋白激酶Ⅱδ

DOI：10.3969/j.issn1008-0392.2012.04.002

基金项目:国家自然科学基金（81170224,81100124)；教育部创新团队计划（1508144002)；上海市浦东新区卫生系统优秀青年医学人才培养项目（PWRq 2011-05)

Modulation of cardiac force-frequency response by dynamin

YE Jiang-chuan^1,2,LIU Ban^1,2,LI Jun^1,2,CHEN Yi-han^1,2

()

Abstract:

Objective To investigate the effect of dynamin2 (DNM2) on cardiac force-frequency response (FFR) . Methods Myocardial cells were isolated from the rat heart and cultured in serum-free media. The recombinant adenovirus containing dominant negative mutant of DNM2 gene (Adv-DNM2K44A ) was transfected into rat cardiomyocytes. Expression and phosphorylation of phospholanbam and activity of Ca2+ -calmodulin dependent protein kinase I 8 (CaMK I 8) was assayed by Western blotting. Pharmacological intervention of DNM2 GTPase was adopted to observe DNM2 regulation of FFR in isolated rat heart. Results The dominant negative mutation DNM2 dampened frequency-dependent increase of fractional shortening and calcium transient in cardiomyocytes，which was related to increased calcium level and CaMK I 8 activation. Furthermore， ex vivo FFR was suppressed by pharmacological inhibition of DNM2 GTPase. Conclusion DNM2 is required for maintenance of normal cardiac FFR and may become a novel pharmacological target for treating heart diseases.

Key words: dynamin force-frequency response calcium level phospholanbam calcium-calmodulin dependent protein kinase II delta