Block of neuronal chloride channels by tetraethylammonium ion derivatives.
Block of neuronal chloride channels by tetraethylammonium ion derivatives.
复制标题
DOI：
10.1085/jgp.106.5.1031
复制
发表时间：
1995-11
影响因子：
3.8
通讯作者：
BLATZ, AL
中科院分区：
文献类型：
--
作者：
SANCHEZ, DY;BLATZ, AL
采用膜片钳技术研究了对称四乙基铵（TEA）离子衍生物四丙基铵（TPrA）、四丁基铵（TBA）和四戊基铵（TPeA）离子对急性解离大鼠皮质神经元快速氯离子通道的阻断作用。当应用于胞内膜表面时，所有三种季铵化合物（QAs）都以与阻断机制一致的方式诱导短暂封闭状态的出现，其中阻断剂优先结合开放的动力学状态并完全阻断通过通道的离子电流。在通道恢复封闭状态之前，药物必须离开通道。采用一维停留时间分析方法研究了堵塞机理。采用Q-矩阵法拟合了动力学模型对开、闭区间持续时间的分布。所有三种QAs的阻断速率常数相似，值约为12-20 x 10(6) M-1s-1。解封率取决于QA的大小或疏水性，最小的衍生物TPrA诱导阻塞状态，平均寿命约为90微秒，而最疏水的衍生物TPeA诱导阻塞状态，平均寿命约为1毫秒。因此，这些氯离子通道的季铵离子阻滞似乎与这些化合物对许多钾离子通道的阻滞几乎相同。这表明阴离子和阳离子可渗透通道之间的传导途径在结构上一定有相似性。
The block by the symmetric tetraethylammonium (TEA) ion derivatives tetrapropylammonium (TPrA), tetrabutylammonium (TBA), and tetrapentylammonium (TPeA) ions of fast chloride channels in acutely dissociated rat cortical neurons was studied with the excised inside- out configuration of the patch-clamp technique. When applied to the intracellular membrane surface, all three of the quaternary ammonium compounds (QAs) induced the appearance of short-lived closed states in a manner consistent with a blocking mechanism where the blocker preferentially binds to the open kinetic state and completely blocks ion current through the channel. The drug must leave the channel before the channel can return to a closed state. The mechanism of block was studied using one-dimensional dwell-time analysis. Kinetic models were fit to distributions of open and closed interval durations using the Q- matrix approach. The blocking rate constants for all three of the QAs were similar with values of approximately 12-20 x 10(6) M-1s-1. The unblocking rates were dependent on the size or hydrophobicity of the QA with the smallest derivative, TPrA, inducing a blocked state with a mean lifetime of approximately 90 microseconds, while the most hydrophobic derivative, TPeA, induced a blocked state with a mean lifetime of approximately 1 ms. Thus, it appears as though quaternary ammonium ion block of these chloride channels is nearly identical to the block of many potassium channels by these compounds. This suggests that there must be structural similarities in the conduction pathway between anion and cation permeable channels.
登录
查看更多内容
神经元快速氯化物通道的块由四乙基铵离子内部。
影响因子：
3.8
作者：
SANCHEZ, DY;BLATZ, AL
通讯作者：
BLATZ, AL
DOI：
10.1085/jgp.58.4.413
发表时间：
1971-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Armstrong CM
通讯作者：
Armstrong CM
影响因子：
3.4
作者：
FRENCH, RJ;SHOUKIMAS, JJ
通讯作者：
SHOUKIMAS, JJ
影响因子：
56.9
作者：
MACKINNON, R;YELLEN, G
通讯作者：
YELLEN, G
影响因子：
5.5
作者：
BLATZ, AL;MAGLEBY, KL
通讯作者：
MAGLEBY, KL