MECHANISMS OF THE VOLTAGE-DEPENDENT SODIUM CHANNEL

一个跨学科的方法将被用来阐明结构和 电压依赖性钠通道的功能。 Electrophorus 电沉积 将采用生物化学方法研究 河豚毒素和石房蛤毒素对钠通道的一种成分，以及因子 影响毒素结合的平衡和动力学结合参数， 将测定和比较完整的膜和洗涤剂提取物。 这 希望能增加我们对毒素分子本质的了解 结合位点，并帮助确定其与通道组分的关系 负责离子选择性。 免疫学方法将用于 确定纯化的河豚毒素/石房蛤毒素结合位点是否与 具有负责其它通道功能的分子结构，例如 电压敏感门控 抗体将被提升到纯化的毒素位点， 目的是产生生理活性抗体， 钠通道位点。 这种抗体可以用作化学探针和标记 与之相关的各种钠通道功能， 相应的结构，并作为一种手段，以确定钠通道在某些 自身免疫性神经肌肉疾病 电生理学方法，主要是 电压钳研究，将被用来确定功能的影响， 免疫和生化化合物。

An interdisciplinary approach will be used to elucidate the structure and function of the voltage-dependent sodium channel from E. electrophorus electroplax. Biochemical methods will be employed to study the binding of tetrodotoxin and saxitoxin to a component of the sodium channel, and factors affecting the equilibrium and kinetic binding parameters of toxin-binding in intact membranes and detergent extracts will be determined and compared. This will hopefully increase our understanding of the molecular nature of the toxin binding site, and help determine its relationship to the channel component responsible for ion selectivity. Immunological methods will be used to ascertain whether the purified tetrodotoxin/saxitoxin binding site is associated with molecular structures responsible for other channel functionalities, such as voltage-sensitive gating. Antibodies will be raised to purified toxin sites, with the goal of generating physiologically-active antibodies affecting other sodium channel sites. Such antibodies could be used chemical probes and labels with which to correlate various sodium channel functions with their corresponding structures, and as a means to determine sodium channel in certain autoimmune neuromuscular diseases. Electrophysiological methods, mainly voltage-clamp studies, will be used to determine the functional affects of immunological and biochemical compounds.