We have developed a genetically encoded bioluminescent indicator for the Na+ channel, in which Na+-sensitive Gaussia luciferase is fused with the voltage-gated Na+ channel. This indicator is capable of detecting Na+ flow through the pores of Na+ channels. Because of high sensitivity and low background in luminescence assays, the absence of toxicity, and a wide linear dynamic range, this luciferase can be used to generate a novel, genetically encoded Na+ channel indicator. It may provide a high-throughput screening system for drug discovery against Na+ channels, which should be useful in controlling lethal cardiac arrhythmias, epileptic seizures, and intolerable pain associated with terminal stages of cancer. It may also offer a system for monitoring the