TRANSIENT INWARD CURRENT UNDERLYING ARRHYTHMOGENIC EFFECTS OF CARDIOTONIC STEROIDS IN PURKINJE-FIBERS
TRANSIENT INWARD CURRENT UNDERLYING ARRHYTHMOGENIC EFFECTS OF CARDIOTONIC STEROIDS IN PURKINJE-FIBERS
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DOI：
10.1113/jphysiol.1976.sp011622
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发表时间：
1976-01-01
影响因子：
5.5
通讯作者：
TSIEN, RW
中科院分区：
文献类型：
--
作者：
LEDERER, WJ;TSIEN, RW
在小牛浦肯野纤维中进行电压钳实验，以确定与洋地黄诱导的心律失常相关的瞬时去极化（TD）的基础。在毒毛旋花子苷的影响下，去极化钳脉冲之后是一个短暂的内向电流（TI），在未处理的制剂中很小或不存在。TI也出现在一系列动作电位之后。它被命名为TI，因为它的大小和时间都适合于解释TD。用2个电压记录微电极测定TI期间的纵向电压不均匀性。虽然不均匀性不严重，但当使用电压差信号测量膜电流密度时，观察到TI波形。在舒张期范围内的潜力，毒毛旋花子苷诱导的TI出现叠加在正常的起搏器机制，衰减的K电流，iK 2。然而，TI可以通过其不寻常的动力学性质从iK 2中解离出来。也可以在保持电位为正至-55 mV时记录TI，即，在iK 2失活发生的范围之外。TI幅度表现出缓慢和强烈的S形依赖于前一个去极化脉冲的持续时间。较强的去极化使TI幅度增大，发展速度加快。冷却降低了TI幅度，同时减缓和夸大了S形时间依赖性。两个钳位脉冲在密切的连续性，在唤起随后的TI的添加剂的效果。这一发现和S形时间依赖性与先前的观察结果相吻合，即TD在一系列紧密间隔的动作电位之后最为突出。TI可以帮助产生自发去极化的制剂，显示低电压振荡，经常发生与先进的洋地黄毒性。
Voltage-clamp experiments were carried out in calf Purkinje fibers to determine the basis of transient depolarizations (TDs) associated with digitalis-induced arrhythmias. Under the influence of strophanthidin, depolarizing clamp pulses were followed by a transient inward current (TI) which was small or absent in untreated preparations. The TI also appeared in the wake of a train of action potentials. It was designated TI because its magnitude and timing were appropriate to account for the TD. Longitudinal voltage non-uniformity during the TI was determined with 2 voltage-recording micro-electrodes. Although the non-uniformity was not severe, the TI wave form was observed when the voltage difference signal was used to measure membrane current density. Over the diastolic range of potential, the strophanthidin-induced TI appeared superimposed upon the normal pace-maker mechanism, the decay of a K current, iK2. The TI could be dissociated from iK2, however, by means of its unusual kinetic properties. TIs could also be recorded at holding potentials positive to -55 mV, i.e., outside the range where iK2 deactivation occurs. The TI amplitude showed a slow and strongly sigmoid dependence on the duration of the preceding depolarizing pulse. Stronger depolarizations increased the TI amplitude and speeded its development. Cooling reduced the TI amplitude, while slowing and exaggerating the sigmoid time-dependence. Two clamp pulses in close succession gave additive effects in evoking a subsequent TI. This finding and the sigmoid time-dependence fit with previous observations that TDs are most prominent following a series of closely spaced action potentials. The TI can help generate spontaneous depolarizations in preparations showing the low voltage oscillations which often occur with advanced digitalis toxicity.