Osteoclasts "sense" elevated extracellular calcium, which leads to cytoskeletal changes that may be linked to phospholipase C (PLC) activation and the associated rise in intracellular calcium ([Ca 2ϩ ] i ). Since PLC is linked to transient receptor potential channels (trp), we hypothesized that receptor activated calcium influx due to this channel type would be activated by osteoclasts sensing [Ca 2ϩ ] e . We found that high [Ca 2ϩ ] e induced similar intracellular Ca 2ϩ rises in chicken

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... asts with or without intracellular Ca 2ϩ store depletion by either TPEN or thapsigargin, thus defining store-insensitive Ca 2ϩ in-flux. This store-insensitive calcium sensing component was blocked by the PLC antagonist U73122. Also, the calcium channel inhibitor SKF 96365, a blocker of store-independent trp-like channels, was effective in inhibiting calcium sensing in the presence of thapsigargin. Thus, a store-independent component of calcium sensing was associated with ion channels linked to PLC. Since receptor activated transient receptor potential (trp) family cation channels open in a PLC-dependent and store-independent manner, we suggest that receptor operated channels are activated in osteoclasts stimulated by high extracellular Ca 2ϩ . (Endocrinology 142: 1968(Endocrinology 142: -1974(Endocrinology 142: , 2001 Preparation of avian osteoclasts Avian osteoclasts were prepared as described previously in accordance with protocols approved by the Animal Studies Committee of the Washington University School of Medicine (16). Briefly, osteoclast pre-