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心律失常发生在各种细胞内钙增加的情况下 ,包括心肌缺血 ,强心甙中毒 ,充血性心衰以及各种原因所致动作电位时程过度延长 .多功能钙 /钙调蛋白依赖性蛋白激酶Ⅱ (钙调蛋白激酶 )是细胞内钙的重要生理靶位和参与调节细胞内钙稳态的关键控制因素 ,包括L型钙电流 ,肌浆网钙释放和摄取 .由于钙调蛋白激酶能影响各种钙敏感离子电流及导致心律失常 ,有可能是一种有效的抗心律失常药物作用靶位 .瞬态内向电流激发迟后除极 ,有可能是钙超负荷心律失常的原因 .有关瞬态内向电流的实质仍有争议 ,但似乎在不同的实验条件下 ,是由不同的离子电流所引起 .这些电流多由细胞内钙激活 ,因为瞬态内向电流总是随着细胞内钙增加而产生 .我们的研究表明在兔心室细胞有三种钙敏感电流有可能与瞬态内向电流产生有关 ,它们是钠 /钙交换电流 ,钙激活的氯电流以及钙激活的非选择性阳离子电流 .我们还发现在生理溶液条件下产生的瞬态内向电流可被钙调蛋白激酶抑制肽所抑制 .我们的实验结果支持这一假说 :钙调蛋白激酶能增强临床相关条件下的瞬态内向电流 ,即细胞内钙增加条件下的瞬态内向电流 ,因而发挥一个致心律失常信号分子的作用
Arrhythmia occurs when various intracellular calcium is increased, including myocardial ischemia, cardiac glycoside poisoning, congestive heart failure, and prolonged action potential duration due to a variety of causes. Multifunctional Calcium / Calmodulin Dependence Protein kinase II (CaMK) is an important physiological target for intracellular calcium and a key control factor involved in the regulation of intracellular calcium homeostasis, including L-type calcium currents, calcium release and uptake in sarcoplasmic reticulum, Can affect a variety of calcium-sensitive ion currents and lead to arrhythmia, may be an effective target of anti-arrhythmic drugs target. Transient inward current excitation delayed depolarization, may be the cause of calcium overload arrhythmias. The nature of the transient inward current remains controversial, but appears to be caused by different ion currents under different experimental conditions, and these currents are mostly activated by intracellular calcium because the transient inward current always increases with increasing intracellular calcium Our study shows that there are three calcium-sensitive currents in rabbit ventricular cells that may be related to transient inward current generation, which are sodium / calcium exchange currents, calcium-activated chloride currents Calcium-activated non-selective cation current We also found that the transient inward current produced under physiological conditions can be inhibited by calmodulin kinase inhibitors Our experimental results support the hypothesis that calmodulin kinase enhances clinical Transient inward current under relevant conditions, ie, transient inward current under increased intracellular calcium, thus exerting a pro-arrhythmic signaling molecule effect