Moczydlowski E, Lucchesi K, Ravindran A
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Membr Biol. 1988 Oct;105(2):95-111. doi: 10.1007/BF02009164.
Voltage-dependent ion channels are a difficult class of proteins to approach biochemically. Many such channels are present at low density in relevant tissues and exist as multiple subtypes that can be distinguished electrophysiologically. In particular, K channels appear to be a diverse family of proteins characterized by many different conductance properties, gating behaviors and regulatory phenomena. Fortunately, specific peptide toxins for K channels are present in the venoms of insects, scorpions, snakes and possibly other species. The available sequences of these peptides define several different families of toxins. Electrophysiological and radioligand binding studies suggest that these toxins can be used to distinguish subclasses of K channels that share similar toxin binding sites. The growing databank of sequence homologies for both toxins and channels is, in essence, a codebook for identifying common elements of structure and function. The continuing development of toxins as biochemical probes should help to uncover the molecular basis and physiological significance of K-channel diversity.
电压依赖性离子通道是一类难以通过生化方法研究的蛋白质。许多这类通道在相关组织中的密度较低,并且以多种亚型的形式存在,这些亚型可以通过电生理学方法加以区分。特别是,钾通道似乎是一个多样化的蛋白质家族,其特征在于许多不同的电导特性、门控行为和调节现象。幸运的是,昆虫、蝎子、蛇以及可能其他物种的毒液中存在针对钾通道的特异性肽毒素。这些肽的现有序列定义了几个不同的毒素家族。电生理学和放射性配体结合研究表明,这些毒素可用于区分具有相似毒素结合位点的钾通道亚类。毒素和通道的序列同源性数据库不断增长,从本质上讲,这是一本用于识别结构和功能共同要素的密码本。将毒素持续开发为生化探针应有助于揭示钾通道多样性的分子基础和生理意义。