Development and Validation of a Thallium Flux-Based Functional Assay for the Sodium Channel NaV1.7 and Its Utility for Lead Discovery and Compound Profiling

Ion channelsare critical for life, and they are targets of numerous drugs. The sequencing of the human genome has revealed the existence of hundreds of different ion channelsubunits capable of forming thousands of ion channels. In the face of this diversity, we only have a few selective small-molecule tools to aid in our understanding of the role specific ion channelsin physiology which may in turn help illuminate their therapeutic potential. Although the advent of automated electrophysiology has increased the rate at which we can screen for and characterize ion channelmodulators, the technique’s high per-measurement cost and moderate throughputcompared to other high-throughput screeningapproaches limit its utility for large-scale high-throughput screening. Therefore, lower cost, more rapid techniques are needed. While ion channeltypes capable of fluxing calcium are well-served by low cost, very high- throughputfluorescence-based assays, other channel typessuch as sodium channelsremain underserve...