The osteoclast Ca²⁺ receptor is highly sensitive to activation by transition metal cations

We report changes in the cytosolic Ca²⁺ concentration ([Ca²⁺]_i) of single rat osteoclasts in response to Ca²⁺ receptor activation by micromolar concentrations of the transition metal cations, Cd²⁺ and Ni²⁺. The extracellular application of Cd²⁺ or Ni²⁺ resulted in a concentration-dependent elevation of cytosolic [Ca²⁺]. Each monophasic [Ca²⁺]_i response consisted of an initial rapid rise of [Ca²⁺]_i to a peak value followed by an exponential decay. Prior application of Cd²⁺ or Ni²⁺ induced refractoriness to a second application of the same cation. The results confirm the existence of a divalent cation-sensitive site on the osteoclast showing features of concentration-dependent activation and use-dependent inactivation.