Structure and Function of the Human 1.8 Voltage-Gated Sodium Channel Associated with Pain Sensation

电压门控钠通道在神经组织的信号传导过程中起着至关重要的作用。人体钠通道（异构体8）主要存在于周围神经系统中，在健康机体中负责疼痛感觉。它的突变会导致一系列疾病，包括慢性疼痛和某些类型的多发性硬化症。该项目的目的是确定这种蛋白质（及其与药物和天然毒素的复合物）的三维结构，并将这些结构与不同疾病状态相关的突变引起的功能特性和构象变化联系起来。这些研究不仅将提供这些疾病的分子基础信息，而且还有助于开发专门针对这种通道类型的新药，从而减少由于与其他通道的意外相互作用而产生的副作用。

Voltage-gated sodium channels play essential roles in the process of signal conduction in nervous tissues. The human sodium channel (isoform 8) is primarily found in the peripheral nervous system, and in the healthy organism is responsible for pain sensation. Mutations in it cause a range of diseases, including chronic pain and certain types of multiple sclerosis. The aim of this project is to determine the three-dimensional structure of this protein (and its complexes with drugs and naturally-occuring toxins), and relate these structures to its functional properties and conformational changes which result from mutations associated with different disease states. These studies will not only provide information on the molecular basis of these diseases but also aid in the development of new pharmaceutical drugs that specifically target this channel type, leading to fewer side-effects due to adventitious interactions with other channels.