MCI-154对大鼠心肌细胞的变力作用(英文)  

Inotropic effects of MCI-154 on rat cardiac myocytes

作　　者：陈还珍[1] 崔香丽[1] 赵画晨[1] 赵录英[1] 吕吉元[1] 吴博威[1] 

机构地区：[1]山西医科大学生理教研室,太原030001

出　　处：《生理学报》2004年第3期301-305,共5页Acta Physiologica Sinica

摘　　要：钙增敏剂具有正性肌力作用,同时不增加细胞内钙浓度,因此可避免导致心律失常和最终心肌细胞死亡的钙超载。然而大部分钙增敏剂对心肌舒张功能有损害作用。MCI-154是一种钙增敏剂,但不损害舒张功能。为阐明其变力作用机制,我们应用离子成像技术研究了MCL-154对分离的单个大鼠心室肌细胞钙瞬变和收缩的影响,利用膜片钳技术观察了MCL-154对大鼠心室肌细胞L-型钙电流和Na^+/Ca^(2+)交换电流的影响。结果表明:(1)MCI-154在1μmol/L至100μmol/L的浓度范围内对L-型钙电流(I_(Ca-L))无直接影响;(2)MCI-154在轻微增加钙瞬变幅度和缩短心肌钙瞬变TR_(50)和TR_(90)的情况下,呈剂量依赖性地增加大鼠心室肌细胞的缩短;(3)MCI-154剂量依赖性地增加正常大鼠心室肌细胞的Na^+/Ca^(2+)交换电流。这些结果提示:MCI-154不仅剂量依赖性地发挥了正性变力作用,对舒张功能也没有损害作用,明显不同于其它钙增敏剂,而且还轻微改善了大鼠心室肌细胞的舒张。其对内向Na^+/Ca^(2+)交换电流的激动作用会加快钙内流,导致TR_(50)和TR_(90)的缩短,提示MCI-154是通过正向Na ^+/Ca^(2+)交换改善舒张功能的。Calcium sensitizers exert positive inotropic effects without increasing intracellular Ca^(2+). Thus, they avoid the undesired effects of Ca^(2+) overload such as arrhythmias and cell injury, but most of them may impair myocyte relaxation. However, MCI-154, also a calcium sensitizer, has no impairment to cardiomyocyte relaxation. To clarify the underlying mechanisms, we examined the effects of MCL-154 on Ca^(2+) transient and cell contraction using ion imaging system, and its influence on L-type Ca^(2+) current and Na^+/Ca^(2+) exchange current with patch clamp technique in rat ventricular myocytes as well. The results showed that: (1) MCI-154 (1～100μmol/L) had no effect on L-type Ca^(2+) current; (2) MCI-154 concentration-dependently increased cell shortening from 5.00±1.6μm of control to 6.2±1.6μm at lμmol/L, 8.7±1.6μm at 10μmol/L and 14.0±1.4μm at 100μmol/L, respectively, with a slight increase in Ca^(2+) transient amplitude and an abbreviation of Ca^(2+) transient restore kinetics assessed by time to 50% restore (TR_(50)) and time to 90% restore (TR_(90)); (3) MCI-154 dose- dependently increased the electrogenic Na^+/Ca^(2+) exchange current both in the inward and the outward directions in rat ventricular myocytes. These results indicate that MCI-154 exerted a positive inotropic action without impairing myocyte relaxation. The stimulation of inward Na^+/Ca^(2+) exchange current may accelerate the Ca^(2+) efflux, leading to abbreviations of TR_(50). and TR_(90) in rat myocytes. The findings suggest that the improvement by MCI-154 of myocyte relaxation is attributed to the forward mode of Na^+/Ca^(2+) exchange.

关 键 词：MCI-154 钙增敏剂 FURA-2 钙瞬变 收缩 L-型钙电流(ICa-L) NA^+/CA^2+交换 膜片钳 

分 类 号：Q27[生物学—细胞生物学] Q426