The beta 1 sodium channel subunit modifies the interactions of neurotoxins and local anesthetics with the rat brain IIA alpha sodium channel in isolated membranes but not in intact cells
The beta 1 sodium channel subunit modifies the interactions of neurotoxins and local anesthetics with the rat brain IIA alpha sodium channel in isolated membranes but not in intact cells
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DOI：
10.1016/0028-3908(96)84631-4
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发表时间：
1996-05-01
影响因子：
4.7
通讯作者：
Hunter, JC
中科院分区：
文献类型：
--
作者：
Bonhaus, DW;Herman, RC;Hunter, JC
哺乳动物脑钠通道由一个α亚基和两个较小的β亚基组成。使用稳定表达人β 1和大鼠脑IIA α亚基的细胞系检查β 1亚基在调节这些通道的配体相互作用中的作用。β 1亚基的共表达对钠通道阻滞剂抑制全细胞[H-3]Batrachotoxinin A benzoate（[H-3]BTX）结合或藜芦碱刺激的[C-14]胍内流的效力没有影响。β 1亚基的共表达对α蝎毒素、短尾蝎毒素或RU 39568刺激[C-14]胍内流的效力也没有影响。相比之下，β 1亚基的共表达对分离膜中的配体相互作用有显著影响。在仅表达α亚基的细胞的分离膜中，神经毒素对[H-3]BTX结合没有刺激作用，并且局部麻醉剂样通道抑制剂的效力比天然钠通道低10-100倍。而在共表达β 1亚基的细胞膜中，神经毒素使[H-3]BTX结合增加30倍，钠通道抑制剂的效力与天然钠通道中发现的效力密切匹配。这些发现表明β 1亚基不是钠通道激活剂或抑制剂结合所必需的，而是β 1亚基可以使α亚基稳定在功能构象中，从而允许在破坏的膜中检测这些相互作用。版权所有（C）1996 Elsevier Science Ltd.
Mammalian brain sodium channels consist of an alpha subunit and two smaller beta subunits. The role of the beta 1 subunit in modulating ligand interactions at these channels was examined using a cell line stably expressing human beta 1 and rat brain IIA alpha subunits. Coexpression of the beta 1 subunit had no effect on the potencies of sodium channel blockers in inhibiting whole cell [H-3]batrachotoxinin A benzoate ([H-3]BTX) binding or veratridine-stimulated [C-14]guanidinium influx. Coexpression of the beta 1 subunit also had no effect on the potencies of alpha scorpion toxin, brevetoxin, or RU 39568 in stimulating [C-14]guanidinium influx. By contrast, coexpression of the beta 1 subunit had dramatic effects on ligand interactions in isolated membranes. In isolated membranes of cells expressing only the alpha subunit, the neurotoxins had no stimulatory effect on [H-3]BTX binding and the potencies of local anesthetic-like channel inhibitors were 10-100-fold lower than those at native sodium channels. Whereas in membranes of cells coexpressing the beta 1 subunit, the neurotoxins increased [H-3]BTX binding 30-fold and the potencies of the sodium channel inhibitors closely matched those found at native sodium channels. These findings indicate that the beta 1 subunit is not required for the binding of sodium channel activators or inhibitors but rather, that the beta 1 subunit may stabilize the alpha subunit in a functional conformation thereby allowing detection of these interactions in disrupted membranes. Copyright (C) 1996 Elsevier Science Ltd.