Comparison of effects of ryanodine and caffeine on rat ventricular myocardium.
Comparison of effects of ryanodine and caffeine on rat ventricular myocardium.
复制标题
兰尼定和咖啡因对大鼠心室心肌的影响比较。
DOI：
10.1152/ajpheart.1986.250.5.h786
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Lakatta,EG
中科院分区：
文献类型：
--
作者：
Sutko,JL;Thompson,LJ;Kort,AA;Lakatta,EG
赖诺定和咖啡因有减少心肌细胞肌浆网（SR）钙释放的能力。为了确定这些药物是否也具有共同的作用机制，我们使用两种不同的实验方法比较了它们对大鼠乳头肌的影响。首先，使用Jundt等人（19）的方案，将静止的大鼠乳头肌暴露于无钠溶液中，我们发现1微米的ryanodine会降低静息力、磷酸化酶α活性以及由于钙依赖性肌丝相互作用导致的散射光强度波动（SLIF）。相比之下，10-20 mM的咖啡因增加了静息力和磷酸化酶α水平，并先增加后降低SLIF至可检测水平以下。在第二个系列实验中，将大鼠乳头肌暴露于125 mM KCl中引起挛缩。ryanodine（1微米）或咖啡因（10毫米）预处理消除了这种反应的初始相成分，同时增加了随后的强补成分。这些作用不同于异丙肾上腺素降低强直性挛缩力的作用。ryanodine对肌力的抑制作用在125 mM KCl溶液中比在正常缓冲液中发展得更快，这表明该药物的负性肌力作用可能部分依赖于膜去极化。这些实验结果表明，ryanodine和咖啡因通过不同的作用机制影响SR钙的释放。赖诺定似乎减少，而咖啡因最初增加，细胞质钙。一旦这些作用发生，这两种药物产生的SR功能的改变同样可以改变其他的肌力反应。
Ryanodine and caffeine have the ability to diminish sarcoplasmic reticulum (SR) calcium release in cardiac muscle cells. To determine whether these agents also share a common mechanism of action, we compared their effects on rat papillary muscles using two different experimental approaches. First, using the protocol of Jundt et al. (19), in which quiescent rat papillary muscles were exposed to sodium-free solutions, we found that 1 microM ryanodine decreased resting force, phosphorylase alpha activity, and the scattered light intensity fluctuations (SLIF) due to calcium-dependent myofilament interactions. In contrast, 10-20 mM caffeine increased both resting force and phosphorylase alpha levels and initially increased then decreased SLIF to below detectable levels. In a second series of experiments, contractures were elicited by exposing rat papillary muscles to 125 mM KCl. Pretreatment with ryanodine (1 microM) or caffeine (10 mM) abolished the initial phasic component of this response, while increasing the subsequent tonic component. These effects were different from those of isoproterenol, which decreased tonic contracture force. The depression of twitch force produced by ryanodine developed more rapidly in the presence of 125 mM KCl than in normal buffer, suggesting that the negative inotropic effects of this agent may, in part, depend on membrane depolarization. The results of these experiments suggest that ryanodine and caffeine affect SR calcium release through different mechanisms of action. Ryanodine appears to decrease, while caffeine initially increases, cytoplasmic calcium. Once these effects have occurred, the alterations of SR function produced by both agents can similarly alter other inotropic responses.