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Effects of Chan Su, a traditional Chinese medicine, on the calcium transients of isolated cardiomyocytes: cardiotoxicity due to more than Na, K-ATPase blocking.

机译:中成药Chan Su对离体心肌细胞钙瞬变的影响:由于Na,K-ATPase的阻滞作用而导致的心脏毒性。

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摘要

Extracts of Chan Su, a traditional Chinese medication used as a topical anesthetic and cardiac medication, were incubated with cardiomyocytes that had been loaded with a calcium specific fluorescent probe. Calcium transients were measured by real-time fluorescence spectrophotometry following treatment. The transients were rapidly abolished following addition of a moderate concentration of the extract (400 ng/ml), resulting in high levels of intracellular calcium, while the lower amount (40 ng/ml) blocked the sodium-potassium adenosine triphosphatase. Treatments with ouabain and nifedipine were also made, either prior to, or after the addition of the Chan Su, in an attempt to better delineate the site(s) of action. The moderate concentration of Chan Su (400 ng/ml) extract caused the myocytes to cease beating within seconds of addition, even in experiments when saturating concentrations of nifedipine or ouabain had been previously added to the cells. As expected bufalin, the active component of Chan Su has similar effects. Our findings indicate that this compound is extremely cardiotoxic, even in small dose and acts rapidly to alter intracellular calcium stores in cardiomyocytes and possibly acts at sites other than the Na(+)+K(+) ATPase, either directly, or indirectly via changes in calcium concentrations.
机译:将陈苏提取物(一种用作局部麻醉和心脏药物的传统中药)与载有钙特异性荧光探针的心肌细胞孵育。处理后通过实时荧光分光光度法测量钙瞬变。加入适度浓度的提取物(400 ng / ml)后,瞬态被迅速消除,导致细胞内钙水平升高,而较低的量(40 ng / ml)则阻断了钠钾腺苷三磷酸酶。在添加Chan Su之前或之后,还用哇巴因和硝苯地平进行了治疗,以试图更好地划定作用部位。适量的Chan Su(400 ng / ml)提取物使肌细胞在添加后几秒钟内就停止跳动,即使在实验中饱和的硝苯地平或哇巴因浓度已预先添加到细胞中时也是如此。正如蟾蜍灵所预期的,禅苏的活性成分具有相似的作用。我们的发现表明,即使是小剂量,该化合物也具有极强的心脏毒性,可迅速改变心肌细胞内钙的储量,并可能直接或通过改变间接作用于Na(+)+ K(+)ATPase以外的位点。钙浓度。

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