The study of the mechanism and characteristics of triggered-activity

触发活性是心律失常发生的重要细胞因子之一。在不同的实验条件下，膜电位变化产生触发活性的机制不同。为了阐明这些电位变化的性质和离子机制，我们采用微电极技术和单蔗糖间隙电压钳法或全细胞钳法分别对狗、豚鼠、兔和青蛙的心脏细胞进行了检测。在<Ca^(2+)>过载条件下，暴露于低<K^+>，高<Ca^(2+)>溶液中，触发活性是由瞬态内向电流形成的延迟后去极化引起的。从电刺激响应的角度，充分分析了这些延迟后去极化和瞬态内向电流的特征，以及它们的电压和时间依赖性质。这些信息可以作为临床心律失常的诊断线索，但不同于再入或自动性。该研究还发现瞬态内向电流不仅在复极化时被激活，而且在去极化电压时也被激活，反映了<Ca^(2+)>从肌浆网循环释放。通过使用<Ca^(2+)>阻滞剂证明了<Ca^(2+)>通过慢通道内流对瞬态内向电流激活的贡献，它们对诱发心律失常的作用可以通过抑制<Ca^(2+)>电流来解释。电缆分析表明，在延迟后去极化和触发活动的发展过程中，内部纵向电阻增加。研究表明，钡诱导的延迟后退极化和自动性不是由瞬态内向电流的激活引起的，而是由<Ba^(2+)>作用于内向整流器<K^+>电流（<I_(kl)>）引起的。<Ba^(2+)>产生了时间和电压依赖的<I_(kl)>阻断，导致延迟后去极化和自动性。乌头碱是另一种产生延迟后去极化和触发活性的药物。在这种情况下，由乌头碱<Na^+>负载触发的瞬态内向电流被证明是一个促成因素。因此，触发活性不是由单一的离子机制引起的，而是由几种不同的机制引起的，这可能解释了这些心律失常的复杂性质。少

Triggered-activity is one of important cellular factors for the genesis of arrhythmias. The membrane potential changes to produce triggered-activity are brought by several different mechanisms depending on the experimental conditions. To clarify the nature and the ionic mechanism of these potential changes, the microelectrode technique and voltage clamp method of the single sucrose gap or whole-cell clamp were applied to heart cells from dog, guinea pig, rabbit and frog. In the <Ca^(2+)> -overloaded conditions by exposing to the low <K^+> , high <Ca^(2+)> solutions, triggered-activity was caused by delayed afterdepolarization which was formed by the transient inward current. The characteristics of these delayed afterdepolarizations and the transient inward current were fully analyzed in terms of the responses to the electrical stimulation, as well as their voltage and time dependent natures. These informations may be used as diagnostic clues for the clinical arrhythmias based on these … More activities but different from reentry or automaticity. The study also disclosed that the transient inward current was activated not only upon repolarization but also during the depolarizing voltages, reflecting cyclic release of <Ca^(2+)> from the sarcoplasmic reticulum. The contribution of <Ca^(2+)> influx via the slow channel to the activation of the transient inward current was demonstrated by use of the <Ca^(2+)> blockers and their actions on triggered-arrhythmias can be explained by the inhibition of the <Ca^(2+)> current. The increase in the internal longitudinal resistance during the development of the delayed afterdepolarizations and triggered-activity was demonstrated by the cable analysis. The study demonstrated that the barium-induced delayed afterdepolarization and automaticity were not brought by the activation of the transient inward current, but by the <Ba^(2+)> action on the inward rectifier <K^+> current ( <I_(kl)> ). <Ba^(2+)> produced time- and voltage-dependent blockade of <I_(kl)> , which induced the delayed afterdepolarizations and automaticity. Aconitine is another agent to produce delayed afterdepolarizations and triggered-activity. In this case, the transient inward current which was triggered by the <Na^+> loading by aconitine, was shown to be a contributing factor. Therefore, triggered-activity is brought not by a single ionic mechanism, but by several different mechanisms, which may explain complex natures of these arrhythmias. Less