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MCI-154对大鼠心肌细胞的变力作用

陈还珍, 崔香丽, 赵画晨, 赵录英, 吕吉元, 吴博威

山西医科大学生理教研室. 山西, 太原 030001

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MCI-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MCI-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lμmol/L至100μmol/L的浓度范围内对L-型钙电流(ICa-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。

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

Inotropic effects of MCI-154 on rat cardiac myocytes

Chen Huanzhen, Cui Xiangli, Zhao Huachen, Zhao Luying, Lu Jiyuan, Wu Bowei

Department of Physiology, Shanxi Medical University. Taiyuan 030001, China

Abstract

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 MCI-154 on Ca~(2+) transient and cell contraction usingion 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 (1～100 #mu#mol/L) had no effect on L-type Ca~(2+) current; (2) MCI-154 concentration-dependently increased cell shortening from 5.00±1.6 #mu#m of control to 6.2±1.6 #mu#m at 1 #mu#mol/L,8.7±1.6 #mu#m at 10 #mu#mol/L and 14.0±1.4 #mu#m at 100 #mu#mol/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 (TR50) and time to 90% restore (TR90); (3) MCI-154 dosedependently 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+) effiux, 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.

Key words: MCI-154;;Calcium sensitizer;;Fura-2;;Calcium transient;

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引用本文：

陈还珍, 崔香丽, 赵画晨, 赵录英, 吕吉元, 吴博威. MCI-154对大鼠心肌细胞的变力作用[J]. 生理学报 2004; 56 (3): .

Chen Huanzhen, Cui Xiangli, Zhao Huachen, Zhao Luying, Lu Jiyuan, Wu Bowei. Inotropic effects of MCI-154 on rat cardiac myocytes. Acta Physiol Sin 2004; 56 (3): (in Chinese with English abstract).