Calcium handling by the osteoclast

The bone resorbing osteoclast is unique in that it is exposed to unusually high, millimolar, Ca2+ concentrations during resorption. It is generally ac cepted that during this process, osteoclasts can "sense" changes in their a mbient Ca2+ concentration. This triggers a sharp cytosolic Ca2+ elevation t hrough both Ca2+ release and Ca2+ influx. The change in cytosolic Ca2+ is t ransduced finally into an inhibition of bone resorption. We have shown that a type 2 ryanodine receptor isoform is expressed uniquely in the plasma me mbrane and functions as a Ca2+ influx channel, and possibly a Ca2+ sensor. Ryanodine receptors are ordinarily Ca2+ release channels that have a micros omal membrane location in a wide variety of eukaryotic cells including the osteoclasts. However, only recently has it become obvious that ryanodine re ceptors are also expressed in other locations, such as nuclear membranes, a t which site they likely gate nucleoplasmic Ca2+ influx. Nucleoplasmic Ca2, in turn, regulates key nuclear processes, including gene expression and a poptosis. 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 b y the osteoclast to handle high Ca2+ loads during bone resorption.