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Intercellular communication mediated by the extracellular calcium-sensing receptor

Nature Cell Biology volume 2, pages 392–398 (2000)Cite this article

Abstract

Agonist-evoked, intracellular Ca2+-signalling events are associated with active extrusion of Ca2+ across the plasma membrane, implying a local increase in Ca2+ concentration ([Ca2+]) at the extracellular face of the cell. The possibility that these external [Ca2+] changes may have specific physiological functions has received little consideration in the past. Here we show that, at physiological ambient [Ca2+], Ca2+ mobilization in one cell produces an extracellular signal that can be detected in nearby cells expressing the extracellular Ca2+-sensing receptor (CaR), a cell-surface receptor for divalent cations with a widespread tissue distribution. The CaR may therefore mediate a universal form of intercellular communication that allows cells to be informed of the Ca2+-signalling status of their neighbours.

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Figure 1: Fura-2 measurements of [Ca2+]in in HEK-CaR cells grown under polypropylene mesh.
Figure 2: Pseudocolour images of HEK-CaR and BHK-21 cells in co-culture, showing fura-2 ratios.
Figure 3: Fura-2 measurements of [Ca2+]in in co-cultured cells.
Figure 4: Intracellular Ca2+ responses of HEK wild-type and BHK-21 cells in co-culture.
Figure 5: Intracellular Ca2+ responses of HEK-CaR and BHK-21 cells in co-culture.
Figure 6: NPS-R-467 sensitizes the CaR in the presence of reduced ambient [Ca2+].
Figure 7: Effects of extracellular Ca2+ buffers.

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Acknowledgements

We thank S. Quinn for helpful suggestions, and E. Nemeth and NPS Pharmaceuticals for the gift of NPS-R-467. This work was supported by a grant from the Harvard Digestive Diseases centre (to A.M.H.), a Medical Research Entry programme Award from the Medical Research Service of the Veteran’s Administration (to A.M.H.), a grant from the St. Giles Foundation, NIH grants DK48330, DK41415 and DK52005 (to E.M.B.) and NIH grant DK44571-10 (to D.I.S.). A.M.H. was supported by the Brigham Surgical Group Foundation and the Medical Research Service of the Veterans Administration. S.C. received support from the University of Bari and from the C.N.R., Italy.

Correspondence and requests for materials should be addressed to A.M.H.

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Authors and Affiliations

  1. Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston,, 02115, Massahusetts, USA

    Aldebaran M. Hofer, Marc A. Doble & David I. Soybel

  2. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston,, 02115, Massachusetts, USA

    Edward M. Brown

  3. Department of Surgery, West Roxbury VAMC, 1400 VFW Parkway, West Roxbury,, 02132,, Massachusetts, USA

    Aldebaran M. Hofer & David I. Soybel

  4. Dipartimento di Fisiologia Generale ed Ambientale, Universita‘ di Bari, Bari, 70126, Italy

    Silvana Curci

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Correspondence to Aldebaran M. Hofer.

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Hofer, A., Curci, S., Doble, M. et al. Intercellular communication mediated by the extracellular calcium-sensing receptor. Nat Cell Biol 2, 392–398 (2000). https://doi.org/10.1038/35017020

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