卡维地洛对RyR2介导的自发性钙振荡的抑制作用

 目的：探讨并比较卡维地洛和其它β受体阻滞剂对兰尼定受体2（RyR2）介导的自发性钙振荡的抑制作用。方法：采用Flp-In T-REx Core Kit构建可以稳定诱导表达RyR2的HEK293细胞株，采用酶解方法分离大鼠单个心肌细胞。逐步提高细胞外钙离子浓度，诱发细胞自发性钙振荡。单细胞钙影像技术记录并检测卡维地洛等β受体阻滞剂对HEK293细胞株及心肌细胞自发性钙振荡的作用。结果：卡维地洛30 μmol/L可明显抑制心肌细胞和表达RyR2的HEK293细胞株的自发性钙振荡，其抑制率分别为(6530±230)%和(6908±530)%；而美托洛尔、索他洛尔、阿替洛尔等常用的14种β受体阻滞剂对心肌细胞及HEK293细胞株的自发性钙振荡均无明显作用。结论：卡维地洛是唯一可以抑制RyR2介导的自发性钙释放的β受体阻滞剂，这可能是卡维地洛在降低心衰死亡率上优于其它β受体阻滞剂的机制之一。

Effects of carvedilol on RyR2-mediated spontaneous calcium oscillation

AIM：To investigate the effects of carvedilol and other β-blockers on ryanodine receptor 2(RyR2)-mediated spontaneous calcium oscillation.
METHODS：HEK293 cells, which steadily and inducibly expressed RyR2, were generated using the Flp-In T-REx Core Kit. Single rat ventricular myocyte was isolated by the method of collagenase. The extracellular Ca2+ concentration was increased step by step to induce calcium oscillation. Single cell calcium imaging was used to test the effects of carvedilol and other β-blockers on RyR2-mediated spontaneous cal-cium oscillation in cardiac cells and HEK293 cells. RESULTS：Carvedilol at concentration of 30 μmol/L obviously suppressed the spontaneous cal-cium oscillation in cardiac cells and HEK293 cells expressing RyR2. The inhibitory rate was (6530±230)% and (6908±530)%, respectively. Metoprolol and other β-blockers had no effects on spontaneous calcium oscillation in cardiac cells and HEK293 cells. CONCLUSION：Carvedilol is the only β-blocker that suppresses RyR2-mediated spontaneous calcium oscillation. This may be one of the mechanisms that carvedilol is better than other β-blockers in reducing the mortality of heart failure.