Regulation of the CaィイD12+ィエD1 channels of rat osteoclast by the signals of bone resorption and formation

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During bone resorption, osteoclasts are exposed to unusually high ambient CaィイD12+ィエD1. This leads to CaィイD12+ィエD1 influx and CaィイD12+ィエD1 release from intracellular CaィイD12+ィエD1 stores, which result in a sharp cytosolic CaィイD12+ィエD1 increase. Finally, the rise in cytosolic CaィイD12+ィエD1 is transduced into an inhibition of bone resorption. It has been demonstrated that a ryanodine receptor (RyR) isoform, expressed in the osteoclast plasma membrane, functions as a CaィイD12+ィエD1 channel and a CaィイD12+ィエD1 sensor. This hypothesis was suggested by the measurement of cyiosolic CaィイD12+ィエD1 concentration. However, a pathway for the CaィイD12+ィエD1 influx through the plasma membrane of osteoclast has not been identified electrophysiologically. In this study, we measured a current that can carry CaィイD12+ィエD1 in the inside-out patch clamp configuration. The current could be measured by the application of the intracellular solution containing high concentration (0.1 mM) of ruthenium red (RtR) plus 3 mM MgClィイD22ィエD2, while it was blocked by low concentration (10 μ M) of RtR. The equilibrium potential of this current was approximately +5 mV, and the conductances were 20 pS (pipette solution contained 10 mM CaClィイD22ィエD2) and 27pS (60 mM CaClィイD22ィエD2), respectively. These results are consistent with the report that RtR triggered an elevation of cytosolic CaィイD12+ィエD1 concentration only when high concentration of RtR was applied (Adebanjo OA et al. Am J Physiol 270 : F469-F475). Here, we provided evidences using an electrophysiological method that RyR expressed in the plasma membrane of osteoclasts were able to conduct CaィイD12+ィエD1 ions for the first time.