雷诺嗪抑制心肌细胞自发性钙漏机制研究  

Ranolazine prevents spontaneous Ca^(2+) release in a knock-in mouse model with calsequestrin mutation R33Q

作　　者：王光明[1] 林立[2] 吕家高[2] 王琳[2] 阮燕菲[3] 白融[3] 刘念[3] 

机构地区：[1]广东食品药品职业学院中医保健学院,广州510521 [2]华中科技大学同济医学院附属同济医院心血管内科 [3]首都医科大学附属北京安贞医院心内科

出　　处：《临床心血管病杂志》2016年第1期55-58,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金项目(No:81370292);北京市自然科学基金(No:7152049)

摘　　要：目的:探讨雷诺嗪对心肌细胞钙漏的影响及其机制。方法:分离儿茶酚胺敏感性室速转基因小鼠CASQ2R33Q心室肌细胞,应用钙显像技术探讨雷诺嗪对R33Q细胞内钙转运的影响。结果:91%R33Q细胞在30nmol/L异丙基肾上腺素(Iso)刺激下可诱发自发性钙波;10μmol/L雷诺嗪预处理孵育后,仅40%R33Q细胞可被Iso诱发出自发性钙波(P<0.05)。在Iso诱发自发性钙波后,再灌流雷诺嗪,75%的细胞自发性钙波完全被抑制。雷诺嗪对基础状态下心肌细胞的钙瞬变参数无明显作用,但显著抑制Iso所致钙瞬变幅值增高、延缓Iso所致钙瞬变衰减的加速和降低Iso所致肌浆网钙库的增加。在穿孔的R33Q细胞,雷诺嗪对自发性钙火花参数无明显影响。结论:雷诺嗪可以抑制Iso所致的心肌细胞钙漏,其机制与直接阻滞兰尼丁受体无关,雷诺嗪具有β受体阻滞效应是可能机制之一。Objective：To assess the effects of ranolazine on the arrhythmogenesis in isolated CASQ2R33 Q myocytes.Method：Ventricular myocytes were isolated from homozygous CASQ2R33 Q mice.Calcium imaging techniques were used.Result：Isoproterenol（Iso,30nM）elicits spontaneous Ca^2＋ transients（SCaTs）in 91%myocytes.Pretreatment with ranolazine（10μmol/L）significantly prevented Iso induced SCaTs（40%,P〈0.05）.Further,we found that Ran can also significantly abolish Iso induced-SCaTs（6out of 8cells）.Ranolazine partly reversed Iso-induced enhancement of Ca^2＋ handling;while ranolazine did not significantly affect them in absence of Iso.In permeablized myocytes,ranolazine did not influence the parameters of Ca^2＋ sparks.Conclusion：Ranolazine effectively prevents spontaneous Ca^2＋ release in isolated CASQ2R33 Q myocytes induced by Iso,while ranolazine does not influence the Ca^2＋ handling in absence of Iso,suggesting that the underlying mechanism is not associated with the direct blockage of the ryanodine receptor,but instead likely associated with the blockage of beta adrenergic receptor.

关 键 词：雷诺嗪 自发性钙漏 儿茶酚胺 心肌细胞 

分 类 号：R542.2[医药卫生—心血管疾病]