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Effect of molsidomine on basal Ca2+ current in rat cardiac cells.

机译:莫斯多明对大鼠心肌细胞基础Ca2 +电流的影响。

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摘要

To determine the effect of molsidomine, a nitric oxide (NO) donor, on basal L-type Ca2+ current (ICa), the patch-clamp study was performed in single myocytes isolated from rat ventricles. External application of molsidomine (10 nM-100 microM) in the presence of internal Ca2+ (pCa = 6.85) inhibited basal ICa in a concentration-dependent manner. In the absence of internal Ca2+ (pCa = infinity), molsidomine concentration-dependently stimulated basal ICa. These opposite effects of molsidomine on ICa were not found when intracellular cGMP (1 mM) had been increased. Regardless of the presence or absence of internal Ca2+, milrinone application (20 microM) had a stimulatory effect on ICa in the absence of intracellular cGMP. In the continuing presence of milrinone, molsidomine (1-100 microM) at pCa infinity had no significant effect on the milrinone-enhanced ICa which was concentration-dependently inhibited by molsidomine (1-100 microM) at pCa 6.85. These results suggest that the inhibitory and stimulatory effects of molsidomine on basal ICa in the rat cardiac myocytes are related to an activation of the cGMP-dependent protein kinase (cGMP-PK) and an inhibition of the cGMP-inhibited cAMP-phosphodiesterase (PDE), respectively, and that these different actions appear to be mediated by the difference in intracellular Ca2+ levels.
机译:为了确定一氧化氮(NO)供体莫西多明对基础L型Ca2 +电流(ICa)的影响,在从大鼠心室分离的单个肌细胞中进行膜片钳研究。在内部Ca2 +(pCa = 6.85)存在的情况下,外部施用莫斯多明(10 nM-100 microM)以浓度依赖的方式抑制了基础ICa。在不存在内部Ca2 +(pCa =无限大)的情况下,莫斯多明的浓度依赖性地刺激了基础ICa。当细胞内cGMP(1 mM)增加时,未发现莫西多明对ICa的这些相反作用。不论是否存在内部Ca2 +,在不存在细胞内cGMP的情况下,应用米力农(20 microM)都会对ICa产生刺激作用。在米力农的持续存在下,pCa无穷大处的molsidomine(1-100 microM)对米力农增强的ICa没有明显影响,而在浓度为pCa 6.85时,molsidomine(1-100 microM)抑制了浓度。这些结果表明,吗啡胺对大鼠心肌细胞基础ICa的抑制和刺激作用与cGMP依赖性蛋白激酶(cGMP-PK)的激活和cGMP抑制的cAMP-磷酸二酯酶(PDE)的抑制有关。 ,并且这些不同的作用似乎是由细胞内Ca2 +水平的差异介导的。

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