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+).
Bennett
B D
BD
Renal Division, Departments of Medicine and Cell Biology, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Alvarez
U
U
Hruska
K A
KA
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000502:physiology; D002645:Chickens; D005029:Ethylenediamines / Q000494:pharmacology; D005260:Female; D009244:NAD+ Nucleosidase / Q000502:physiology; D010010:Osteoclasts / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015220:Calcium Channels; D005029:Ethylenediamines; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D019284:Thapsigargin; D010738:Type C Phospholipases; D036541:ADP-ribosyl Cyclase; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D002118:Calcium