Two-component blocking kinetics of open NMDA channels by organic cations.
Two-component blocking kinetics of open NMDA channels by organic cations.
复制标题
有机阳离子开放 NMDA 通道的双组分阻断动力学。
DOI：
10.1016/s0005-2736(98)00211-9
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
A. Sobolevsky
中科院分区：
文献类型：
--
作者：
A. Sobolevsky
用全细胞膜片钳技术记录急性分离的大鼠海马神经元NMDA受体通道反应。在天冬氨酸、四乙基铵、四丁基铵、1-氨基-3-丙基金刚烷和9-氨基吖啶的连续存在下，NMDA通道电流发生变化，其变化符合双指数函数。据建立，取决于恢复动力学的快分量的振幅的行为，阻滞剂的作用可以被分配到由最简单的模型所描述的五种类型之一。四乙基铵、四丁基铵和1-氨基-3-丙基金刚烷的作用可以用这些模型很好地描述。使用9-氨基吖啶作为一个例子，它表明，最简单的模型不能描述所有可能类型的阻断剂通道相互作用。在这种情况下，可以使用最简单的模型组合的方法。应用最简单的动力学模型分析可以得出以下结论：至少两个分子的1-氨基-3-丙基金刚烷或9-氨基吖啶可以同时与开放通道结合并阻断通道，9-氨基吖啶阻断通道的位点可以通过至少两种不同的方式进行占据;四丁基铵和9-氨基吖啶的结合阻止了通道的激活和/或脱敏门的关闭，而四乙基铵则没有。
NMDA receptor channel responses were recorded from acutely isolated rat hippocampal neurons, using whole-cell patch-clamp techniques. In the continuous presence of aspartate, tetraethylammonium, tetrabutylammonium, 1-amino-3-propyl-adamantane and 9-aminoacridine caused changes in the current through NMDA channels, which were described by two-exponential functions. It was established that depending on the behavior of the amplitude of the fast component for the recovery kinetics, the blocker action can be assigned to one of five types described by the simplest models. The effects of tetraethylammonium, tetrabutylammonium and 1-amino-3-propyl-adamantane were well described by these models. Using 9-aminoacridine as an example, it was shown that the simplest models cannot describe all possible types of the blocker-channel interaction. In such cases, the method of the simplest models combination can be used. The application of the simplest kinetic models analysis allowed to make the following conclusions: at least two molecules of 1-amino-3-propyl-adamantane or 9-aminoacridine can simultaneously bind to the open channel and block it; the occupation of 9-aminoacridine blocking sites in the channel can proceed in at least two different ways; the binding of tetrabutylammonium and 9-aminoacridine prevented the closure of the activation and/or desensitization gates of the channel, while that of tetraethylammonium did not.
新型金刚烷衍生物可作为开放配体门控通道的阻断剂和抗惊厥药。
DOI：
--
发表时间：
1995
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Antonov,SM;Johnson,JW;Lukomskaya,NY;Potapyeva,NN;Gmiro,VE;Magazanik,LG
通讯作者：
Magazanik,LG