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

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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.