Receptor-operated osteoclast calcium sensing.

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(2+)](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(2+)](e). We found that high [Ca(2+)](e) induced similar intracellular Ca(2+) rises in chicken osteoclasts with or without intracellular Ca(2+) store depletion by either TPEN or thapsigargin, thus defining store-insensitive Ca(2+) influx. 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(2+).