Lithium- Sensitive Store-Operated Ca²⁺ Entry in the Regulation of FGF23 Release

Lithium, a widely used drug for the treatment of mood disorders, has previously been shown to stimulate the release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH)2D3 formation and mineral metabolism. The cellular mechanisms involved have remained elusive. Lithium has been shown to modify Ca2+ signaling. In a wide variety of cells, Ca2+ entry is accomplished by the pore-forming Ca2+ channel subunit Orai1 and its regulator STIM, which stimulates Orai following Ca2+ depletion of intracellular stores. Transcription factors promoting Orai1 expression include NF-κB. The present study thus explored whether the effect of lithium on FGF23 involves and requires Ca2+ entry.