Cell biologists know the calcium ion best as a vital intracellular second messenger that governs countless cellular functions. However, the recent identification of cellsurface detectors for extracellular Ca 2+ has prompted consideration of whether Ca 2+ also functions as a signaling molecule in the extracellular milieu. The cast of Ca 2+ sensors includes the well-characterized extracellular-Ca 2+sensing receptor, a G-protein-coupled receptor originally isolated from the parathyroid gland. In

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... dition, other receptors, channels and membrane proteins, such as gap junction hemichannels, metabotropic glutamate receptors, HERG K + channels and the receptor Notch, are all sensitive to external [Ca 2+ ] fluctuations. A recently cloned Ca 2+ sensor (CAS) in Arabidopsis extends this concept to the plant kingdom. Emerging evidence indicates that [Ca 2+ ] in the local microenvironment outside the cell undergoes alterations potentially sufficient to exert biological actions through these sensor proteins. The extracellular space might therefore constitute a much more dynamic Ca 2+ signaling compartment than previously appreciated.