MECHANISMS OF THE VOLTAGE-DEPENDENT SODIUM CHANNEL

将使用跨学科的方法来阐明结构和 电泳藻电压依赖性钠通道的功能 电浆。生物化学方法将被用来研究结合 河豚毒素和岩藻毒素对钠通道的一种成分，以及因子 影响细菌毒素结合平衡参数和动力学参数的研究 完整的膜和洗涤剂提取物将被测定和比较。这 将有望增加我们对毒素分子性质的了解 结合位点，并帮助确定其与通道组件的关系 负责离子选择性。将使用免疫学方法来 确定纯化的河豚毒素/麻黄毒素结合位点是否相关 具有负责其他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部位， 目标是产生影响其他人的生理活性抗体 钠离子通道位置。这种抗体可用于化学探针和标记 从而将各种钠通道功能与它们的 相应的结构，并作为确定某些特定钠通道的手段 自身免疫性神经肌肉疾病。电生理方法，主要是 电压钳研究，将被用来确定 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.