EARLY AFTERDEPOLARIZATIONS IN CARDIAC MYOCYTES - MECHANISM AND RATE DEPENDENCE
EARLY AFTERDEPOLARIZATIONS IN CARDIAC MYOCYTES - MECHANISM AND RATE DEPENDENCE
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DOI：
10.1016/s0006-3495(95)80271-7
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发表时间：
1995-03-01
影响因子：
3.4
通讯作者：
RUDY, Y
中科院分区：
文献类型：
--
作者：
ZENG, JL;RUDY, Y
采用考虑离子浓度动态变化的心室动作电位模型，研究了早期后去极化（EADs）的机制、特征和速率依赖性。介绍了一种模拟方法来研究药物对细胞过程的影响。模拟结果与实验观察结果在质量上是一致的，并有助于解决文献中关于EADs机制的矛盾结论。结果表明：1)在EAD过程中，l型钙电流I-Ca作为去极化电荷载体是必要的；2) I-Ca的恢复和再激活是EAD形成的机制，与诱导EAD的干预措施无关（我们在模拟中使用了铯、Bay K 8644或异丙肾上腺素，遵循类似的已发表的实验方案）；3) EAD的发展不需要高[Ca2+](i)，并且在EAD期间肌浆网不发生钙释放；4)虽然EAD形成的主要机制是I-Ca的恢复，但在EAD起飞前的一个条件阶段，其他平台电流可以通过影响电流平衡来调节EAD的形成；5)在驱动器周期长度大于1000 ms时存在EADs。由于延迟整流钾电流I-K的激活时间常数非常长，因此在快速连续刺激（驱动周期长度< 1000 ms）之间，I-K的激活门不会完全失活。因此，I-K在决定EADs的速率依赖性方面起着关键作用。
A model of the cardiac ventricular action potential that accounts for dynamic changes in ionic concentrations was used to study the mechanism, characteristics, and rate dependence of early afterdepolarizations (EADs). A simulation approach to the study of the effects of pharmacological agents on cellular processes was introduced. The simulation results are qualitatively consistent with experimental observations and help resolve contradictory conclusions in the literature regarding the mechanism of EADs. Our results demonstrate that: 1) the L-type calcium current, I-Ca, is necessary as a depolarizing charge carrier during an EAD; 2) recovery and reactivation of I-Ca is the mechanism of EAD formation, independent of the intervention used to induce the EADs (cesium, Bay K 8644, or isoproterenol were used in our simulations, following similar published experimental protocols); 3) high [Ca2+](i) is not required for EADs to develop and calcium release by the sarcoplasmic reticulum does not occur during the EAD; 4) although the primary mechanism of EAD formation is recovery of I-Ca, other plateau currents can modulate EAD formation by affecting the balance of currents during a conditional phase before the EAD take-off; and 5) EADs are present at drive cycle lengths longer than 1000 ms. Because of the very long activation time constant of the delayed rectifier potassium current, I-K, the activation gate of I-K does not deactivate completely between consecutive stimuli at fast rates (drive cycle length < 1000 ms). As a result, I-K, plays a key role in determining the rate dependence of EADs.