Modulation of the osteoclast Ca²⁺ receptor by extracellular protons: Possible linkage between Ca²⁺ sensing and extracellular acidification

We report a sensitivity of the osteoclast cell surface Ca²⁺ receptor to extracellular protons. Freshly isolated rat osteoclasts were exposed to the known agonists of the Ca²⁺ receptor, Ca²⁺ and Ni²⁺, in extracellular solutions set at different pH values. Decreasing the extracellular pH from 7.8 to 4.0 units markedly potentiated the cytosolic Ca²⁺ signals elicited in response to Ca²⁺ receptor activation by either Ni²⁺ (50 μM, 500 μM or 5 mM) or Ca²⁺ (5 mM). Each response consisted of a rapid and usually transient elevation of cytosolic [Ca²⁺]. Maximal cytosolic [Ca²⁺] responses were obtained at pH values of 6.6 (for 5 mM-[Ni²⁺]) and 4.0 units (for 5 mM-[Ca²⁺]). Finally, the effects of extracellular pH persisted in Ca²⁺-free, EGTA-containing solutions, suggesting a modulation of intracellular Ca²⁺ release.