FUNCTIONAL CONSEQUENCES OF THE INTERACTION OF NI2+ WITH THE OSTEOCLAST CA2+ RECEPTOR

Ni2+ was used as an extracellular activator of the Ca2+ 'receptor' in order to study the regulation of osteoclast function in vitro. Applica tion of different micromolar concentrations of Ni2+ to osteoclasts bat hed in 1.25 mm [Ca2+] and 0-8 mM [Mg2+] caused a concentration-depende nt elevation of cytosolic [Ca2+] measured in single cells using fura-2 fluorescence. Cytosolic [Ca2+] responses to 5 mm [Ni2+] showed a rapi dly developing and use-dependent inactivation, unlike those induced by the application of 10 mm [Ca2+]. Pre-treatment with 5 mm [Ni2+] reduc ed the magnitude of responses to a subsequent extracellular applicatio n of 10 mM [Ca2+] and vice versa. Ni2+ treatment elicited a number of functional effects. It produced an inhibition of osteoclastic bone res orption which was sustained over hours. This was associated with a pro nounced cell retraction or R effect over the 40 min period following N i2+ exposure as observed by time-lapse video image analysis. Both thes e effects varied with concentration. In contrast, granule movement, ce ll migration, and quantitative indicators of margin ruffling were all unchanged. These findings are consistent with the initiation of a caus ally related set of specific functional and morphometric events follow ing activation of a specific membrane receptor sensitive to divalent c ations.