Rasmusson R L, Zhang Y, Campbell D L, Comer M B, Castellino R C, Liu S, Morales M J, Strauss H C
Department of Biomedical Engineering, Medicine Duke University, Durham, NC 27710, USA.
Adv Exp Med Biol. 1995;382:11-22. doi: 10.1007/978-1-4615-1893-8_2.
We studied the blocking effects of 4-aminopyridine (4-AP) on a Kv1.4 K+ channel. A permanently charged 4-AP derivative only produced block when applied intracellularly. 4-AP block accumulated from pulse to pulse indicating trapping of 4-AP in deactivated channels. For long trains of depolarizing pulses, 4-AP block increased with decreasing pulse duration. This increase took many pulses (> 10) to accumulate and was relieved by two to three subsequent pulses of 500 msec duration. We conclude that the time- and voltage-dependence of 4-AP block can not be accounted for solely by either simple pure open channel or pure closed channel blocking schemes. We propose that the data can be explained by a model in which 4-AP binding is most stable when the channel has a symmetric arrangement in the binding regions.
我们研究了4-氨基吡啶（4-AP）对Kv1.4钾通道的阻断作用。一种带永久电荷的4-AP衍生物仅在细胞内应用时才产生阻断作用。4-AP阻断作用逐脉冲累积，表明4-AP被困在失活通道中。对于长时间的去极化脉冲序列，4-AP阻断作用随脉冲持续时间的缩短而增加。这种增加需要多个脉冲（>10个）才能累积起来，并可通过随后两到三个持续时间为500毫秒的脉冲来缓解。我们得出结论，4-AP阻断的时间和电压依赖性不能仅通过简单的纯开放通道或纯关闭通道阻断机制来解释。我们提出，这些数据可以用一个模型来解释，即在该模型中，当通道在结合区域具有对称排列时，4-AP结合最稳定。
