: The bone resorbing osteoclast is unique in that it is exposed to unusually high, millimolar, Ca2+ concentrations during resorption. It is generally accepted that during this process, osteoclasts can "sense" changes in their ambient Ca2+ concentration. This triggers a sharp cytosolic Ca2+ elevation through both Ca2+ release and Ca2+ influx. The change in cytosolic Ca2+ is transduced finally into an inhibition of bone resorption. We have shown that a type 2 ryanodine receptor isoform is expressed uniquely in the plasma membrane and functions as a Ca2+ influx channel, and possibly a Ca2+ sensor. Ryanodine receptors are ordinarily Ca2+ release channels that have a microsomal membrane location in a wide variety of eukaryotic cells including the osteoclasts. However, only recently has it become obvious that ryanodine receptors are also expressed in other locations, such as nuclear membranes, at which site they likely gate nucleoplasmic Ca2+ influx. Nucleoplasmic Ca2+, in turn, regulates key nuclear processes, including gene expression and apoptosis. Here, we review potential mechanisms underlying the recognition, movement, and effects of Ca2+ in the osteoclast. We will also speculate on the general biological significance of the somewhat unique processes used by the osteoclast to handle high Ca2+ loads during bone resorption.
The Endocrinologist 2000; 10: 155-163
* Review the role of extracellular Ca2+ in regulating osteoclast activity.
* How do osteoclasts "sense" and respond to changes in extracellular Ca2+? How do ryanodine receptors fit into this process?
* Consider the biological meaning of the processes used by osteoclasts to manage a high load of Ca2+ during bone resorption.
(C) 2000 Lippincott Williams & Wilkins, Inc.