Arginine-specific reagents remove sodium channel inactivation
Arginine-specific reagents remove sodium channel inactivation
复制标题
精氨酸特异性试剂消除钠通道失活
作者：
D. Eaton;M. Brodwick;G. Oxford;B. Rudy
蛋白质类通常被认为是可兴奋膜的分子组分，可兴奋膜赋予神经和肌肉细胞电压依赖性渗透性。由于与其他膜组分相比，直接负责离子电导的蛋白质分子的浓度相对较低，因此这些蛋白质的分离、表征和重构仍处于相当早期的阶段。然而，可兴奋组织的电导机制的分子性质的某些方面可以使用特异性修饰蛋白质分子的化学试剂来推导。特别是，钠失活过程可以通过用各种蛋白水解酶处理来消除1 - 3，6。其中，胰蛋白酶可能是最有选择性的，主要在乙酰基或赖氨酰残基4裂解。一些研究人员认为，正是这样一个暴露的带正电荷的残基可能是负责阻断钠电导途径，产生失活5，6。因此，应该可以通过用对所涉及的残基具有特异性的试剂改变封闭残基的构型和/或电荷来改变或消除失活。乙二醛、苯基乙二醛和缩合的2，3-丁二酮是三种这样的试剂，它们与精氨酸的胍基非常反应7 -9。本文介绍了钠失活的影响，这些代理商时，他们内部灌注在鱿鱼轴突。
PROTEINS are often suggested to be the molecular components of excitable membranes which confer voltage-dependent permeability properties on nerve and muscle cells. Because of the relatively low concentration of the protein molecules directly responsible for ionic conductances compared with other membrane components, the isolation, characterisation, and reconstitution of these proteins is still at a rather early stage. Certain aspects of the molecular nature of the conductance mechanisms of excitable tissues, however, can be deduced using chemical reagents which specifically modify protein molecules. In particular, the sodium inactivation process can be eliminated by treatment with various proteolytic enzymes1–3,6. Of these, trypsin is probably the most selective, cleaving mainly at arginyl or lysyl residues4. Several investigators have suggested that just such an exposed positively charged residue might be responsible for blocking the sodium conductance pathway to produce inactivation5,6. Therefore, it should be possible to alter or remove inactivation by changing the configuration and/or charge of the blocking residue with a reagent specific for the residue involved. Glyoxal, phenylglyoxal and condensed 2,3-butanedione are three such reagents which are very reactive with the guanidino group of arginine7–9. This paper describes the effect on sodium inactivation of these agents when they are internally perfused in the squid axon.