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.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
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)
关键词
雷诺嗪
自发性钙漏
儿茶酚胺
心肌细胞
ranolazine
spontaneous Ca^2+ release
catecholamine
cardiac myocytes