Voltage-gated sodium channels (NaV1.X) are essential membrane proteins that initiate and propagate action potentials by mediating rapid sodium influx in response to membrane depolarization. They underlie key physiological processes including neuronal signaling (NaV1.1, NaV1.2, NaV1.6), cardiac conduction (NaV1.5), and pain sensation (NaV1.7–NaV1.9). Abnormal NaV1.X activity is implicated in disorders such as epilepsy, cardiac arrhythmias, and chronic pain, positioning these channels as high-value therapeutic targets. Conventional methods for assessing NaV1.X function such as patch-clamp electrophysiology and radiolabeled ion flux assays are often low-throughput, technically demanding, and reliant on specialized instrumentation. 

ION Biosciences’ Brilliant Lithium Assay overcomes these limitations with a next-generation, fluorescence-based approach for high-throughput screening of NaV1.X channel modulators. The assay uses ION Lithium Green 1 AM (ILG-1 AM), a membrane-permeable, lithium-sensitive fluorescent dye that enables functional NaV1.X channel measurements using lithium as a surrogate ion. Lithium readily permeates open NaV1.X channels while bypassing many endogenous sodium-handling mechanisms, resulting in a robust and selective readout of channel activity. Upon depolarization or pharmacological activation of NaV1.X channels, lithium accumulates intracellularly producing a rapid, quantifiable fluorescence increase that reflects real time channel activity.

Compared to our Brilliant Sodium 2 Assay, Brilliant Lithium delivers approximately a two-fold larger screening window, enhanced assay sensitivity, and a larger dynamic range. This improved performance supports reliable modulator identification in both 96- and 384-well high-throughput screening formats.