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Metabolic Acidosis Increases Intracellular Calcium in Bone Cells Through Activation of the Proton Receptor OGR1
Author(s) -
Frick Kevin K,
Krieger Nancy S,
Nehrke Keith,
Bushinsky David A
Publication year - 2009
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.081015
Subject(s) - calcium , metabolic acidosis , calcium in biology , intracellular , endocrinology , medicine , receptor , chemistry , acidosis , biology , biochemistry
Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein‐coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1 , TDAG8 , G2A , and GPR4 . We tested the hypothesis that the G protein‐coupled proton sensor, OGR1, is an H + ‐sensing receptor in bone. To determine whether acid‐induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium ± the OGR1 inhibitor CuCl 2 . CuCl 2 decreased MET‐induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Ca i . Perfusion with MET induced a rapid, flow‐independent, increase in Ca i in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Ca i in response to H + , we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Ca i in OGR1 ‐transfected CHO cells. These data indicate that OGR1 induces an increase in Ca i in response to MET and is a prime candidate for an osteoblast proton sensor.