Extracellular Ca²⁺ sensing by the osteoclast

An increasing number of cell types appear to detect changes in the extracellular Ca²⁺ concentrationand and accordingly modify their function. We review recent evidence for the existence and function of such a mechanism in the osteoclast. Elevated external [Ca²⁺] in the mM range reduces bone resorption and results in motile changes in the cells. These changes may partly result from elevations of cytosolic [Ca²⁺] triggered through activation of a surface Ca²⁺ receptor. Closer analyses of the increases in cytosolic [Ca²⁺] associated with receptor activation are hindered by the action of this ion both as extracellular agonist and intracellular second messenger. Variations in the peak cytosolic [Ca²⁺] response to external Ca²⁺ with changes in cell membrane potential by K⁺ and valinomycin establish a contribution from extracellular Ca²⁺. Use of CIO₄^-, Ni²⁺ and Cd²⁺ as surrogate activators in low extracellular [Ca²⁺] indicate a contribution from Ca²⁺] release from intracellular stores as well. Such agonists also modify Ca²⁺ redistribution in other systems, such as skeletal muscle. Thus, we may gain insights into osteoclast extra-cellular Ca²⁺ detection and transduction from known features of more well-characterised cell systems.