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首页> 外文期刊>Acta Pharmacologica Sinica >E-4031 enhanced Ca~(2+) transient and ventricular myocytes contraction via reverse mode Na~+/Ca~(2+) exchange in normal and hypertrophic rats
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E-4031 enhanced Ca~(2+) transient and ventricular myocytes contraction via reverse mode Na~+/Ca~(2+) exchange in normal and hypertrophic rats

机译：在正常和肥大大鼠中，E-4031通过逆向Na〜+ / Ca〜（2+）交换增强了Ca〜（2+）瞬时和心室肌细胞的收缩

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摘要

AIM: To study the effects of N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl] methanesulfonamide dihydrochloride dihydrate (E-4031), a specific I_K blocker, on Ca~(2+) transient and cell contraction of normal and hypertrophied rat ventricular myocytes. METHODS: Electrically triggered Ca~(2+) transient and cell shortening were measured simultaneously using the Ion Imaging System with charge coupled digital (CCD) camera. RESULTS: E-4031 (10μmol/L) increased Ca~(2+) transient and cell shortening from (210 +- 49) and (3.0 +- 0.8)μm to (245 +- 47) and (3.6 +- 1.0)μm, respectively (P<0.05) in normal cardiomyocytes and from (196 +- 54) and (3.0 +- 1.3)μm to (240 +- 49) and (3.6 +- 1.3)μm respectively (P<0.05) in hypertrophied cardiomyocytes, while did not change calcium sensitivity in both groups. KB-R7943 completely blocked the activating effects induced by E-4031 in both of normal and hypertrophied cardiomyocytes. Nicardipine did not block the increasing effects of E-4031. CONCLUSION: E-4031 increased Ca~(2+) transient and cell contraction via stimulating reverse mode of Na~+/Ca~(2+) exchange while without influencing calcium sensitivity. These effects were more notable in hypertrophied cardiomyocytes than in normal myocytes.
机译：目的：研究N- [4-[[1- [2-（6-甲基-2-吡啶基）乙基] -4-哌啶基]羰基]苯基]甲磺酰胺二盐酸盐二水合物（E-4031）的作用I_K阻滞剂对正常和肥大大鼠心室肌细胞Ca〜（2+）瞬时表达和细胞收缩的影响。方法：使用带有电荷耦合数字（CCD）相机的离子成像系统同时测量电触发的Ca〜（2+）瞬变和细胞缩短。结果：E-4031（10μmol/ L）使Ca〜（2+）瞬变和细胞缩短从（210 +-49）和（3.0 +-0.8）μm增加到（245 +-47）和（3.6 +-1.0）正常心肌细胞分别为（μm）（μm）（P <0.05），肥厚的心肌细胞分别从（196 +-54）和（3.0 +-1.3）μm到（240 +-49）和（3.6 +-1.3）μm（P <0.05）心肌细胞，但两组均未改变钙敏感性。 KB-R7943完全阻断了E-4031在正常和肥大型心肌细胞中诱导的激活作用。尼卡地平没有阻止E-4031的增加作用。结论：E-4031通过刺激Na〜+ / Ca〜（2+）交换的逆向模式增加Ca〜（2+）的瞬时表达和细胞收缩，而不影响钙敏感性。这些作用在肥厚型心肌细胞中比在正常心肌细胞中更明显。

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