Another dimension to calcium signaling: a look at extracellular calcium

Cell biologists know the calcium ion best as a vital intracellular second messenger that governs countless cellular functions. However, the recent identification of cell-surface detectors for extracellular Ca2+ has prompted consideration of whether Ca2+ also functions as a signaling molecule in the extracellular milieu. The cast of Ca2+ sensors includes the well-characterized extracellular-Ca2+ sensing receptor, a G-protein-coupled receptor originally isolated from the parathyroid gland. In addition, 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 [Ca2+] fluctuations. A recently cloned Ca2+ sensor (CAS) in Arabidopsis extends this concept to the plant kingdom. Emerging evidence indicates that [Ca2+] 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 Ca2+ signaling compartment than previously appreciated.