Binding of GABA receptor channel drugs to a putative voltage-dependent chloride channel in Torpedo electric organ.
Binding of GABA receptor channel drugs to a putative voltage-dependent chloride channel in Torpedo electric organ.
复制标题
GABA 受体通道药物与鱼雷电器官中假定的电压依赖性氯离子通道的结合。
DOI：
10.1016/0006-2952(85)90550-7
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发表时间：
1985
影响因子：
5.8
通讯作者：
Eldefrawi,AT
中科院分区：
文献类型：
--
作者：
Abalis,IM;Eldefrawi,ME;Eldefrawi,AT
在肌肉和神经元细胞中，有两种主要类型的 Cl− 通道：电压依赖性 Cl− 通道，通过跨膜电压的变化激活，对静息膜电导贡献主要份额 (1)；化学操作的 Cl− 通道，是 γ-氨基丁酸 (GABA) 或甘氨酸抑制性受体系统的一部分，通过结合 发射器 (2)。尽管人们对这些受体的生化和药理学性质了解很多，但关于电压依赖性 Cl− 通道的此类信息却很少。当人们发现电射线的电器官（烟碱乙酰胆碱 (ACh) 受体的丰富来源）也可能富含 Cl− 通道时，研究此类通道的机会就变得可行。在鱼雷电器官中发现了阴离子选择性通道，如平面磷脂双层 (3) 和脂质体膜囊泡 (4) 中的重构膜囊泡中阴离子电导的增加所示，以及在 Narke japonica 的电器官中发现的阴离子选择性通道，如渗透体积和 35 SO 4−(5) 流出量的变化所示。这些效应可被特定的 Cl− 通道抑制剂 4, 4'-二异硫氰基-2, 2'-二苯乙烯二磺酸 (DIDS) 抑制。该 Cl− 通道也在青蛙爪蟾卵母细胞中表达，该卵母细胞注射了来自鱼雷电器官的 mRNA 部分，而另一部分 mRNA 则诱导了 ACh 受体的掺入 (6)。与线粒体 Cl− 通道的 2 倍选择性相比，该电器官 Cl− 通道具有高度阴离子选择性（Cl− 的渗透性至少是 K+ 的 20 倍）(3)。本研究旨在尝试识别鱼雷电器官中的 Cl− 通道，使用 [35 S] 叔丁基二环硫代磷酸酯 (TBPS) 作为探针，因为它与 GABA 受体 Cl− 通道具有高亲和力结合 (7)，并确定和比较这些不同类型的 Cl− 通道的药物特异性。
In muscle and neuronal cells, there are two major types of Cl− channels: the voltage-dependent Cl− channels, which are activated by changes in voltage across the membrane and contribute a major share to the resting membrane conductance (1), and the chemically operated Cl− channels which are parts of the inhibitory receptor systems of γ-aminobutyric acid (GABA) or glycine, and are activated by binding of the transmitter (2). Although much is known about the biochemical and pharmacological nature of these receptors, very little such information is available on the voltage-dependent Cl− channels. The opportunity to study one such channel became feasible when it was discovered that the electric organ of electric rays, which is a rich source for nicotinic acetylcholine (ACh) receptors, may also be rich in Cl− channels. An anion-selective channel was discovered in the electric organs of Torpedo californica as shown by increased anion conductance in reconstituted membrane vesicles in planar phospholipid bilayer (3) and in liposomal membrane vesicles (4), and of Narke japonica as shown by changes in osmotic volume and efflux of 35 SO 4−(5). These effects were inhibited by the specific Cl− channel inhibitor 4, 4′-diisothiocyano-2, 2′-stilbenedisulfonic acid (DIDS). This Cl− channel was also expressed in frog Xenopus oocytes that had been injected with mRNA fraction from Torpedo electric organ, while another fraction of mRNA induced the incorporation of ACh receptors (6). This electric organ Cl− channel is highly anion selective (at least 20-fold more permeable to Cl− than to K+) compared to a 2-fold selectivity for a mitochondrial Cl− channel (3). The present study was initiated to attempt identification of the Cl− channel in Torpedo electric organ, using [35 S] t-butylbicyclophosphorothionate (TBPS) as a probe since it binds with a high affinity to the GABA receptor Cl− channel (7), and to determine and compare the drug specificities of these different types of Cl− channels.