title: Another dimension to calcium signaling: a look at extracellular calcium.
abstract: 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 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 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 [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.
authors.affiliation: VA Boston Healthcare System and Brigham & Women's Hospital, Department of Surgery, Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA 02132, USA. ahofer@rics.bwh.harvard.edu
authors.forename: Aldebaran M
authors.initials: AM
authors.lastname: Hofer
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000378:metabolism; D019521:Body Patterning; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D027682:Cation Transport Proteins / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D051638:Ether-A-Go-Go Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism; D017629:Gap Junctions; D006801:Humans; D007477:Ions / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D010280:Parathyroid Glands / Q000378:metabolism; D010944:Plants / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction
chemical_list: D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D007477:Ions; C092509:KCNH6 protein, human; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D018094:Receptors, Metabotropic Glutamate; D051880:Receptors, Notch; D019204:GTP-Binding Proteins; D002118:Calcium