Inhibition of inwardly rectifying K+ current by external Ca2+ ions in freshly isolated rabbit osteoclasts

1. Regulation of membrane potential by extracellular Ca2+ concentration ([Ca2+]o) was examined in freshly isolated rabbit osteoclasts. 2. The resting membrane potential of osteoclasts was close to the K+ equilibrium potential in 1 mM Ca2+ medium. An elevation of [Ca2+]o caused membrane depolarization, accompanied by a decrease in the membrane conductance. 3. The inwardly rectifying K+ current observed under voltage clamp was dose-dependently inhibited by an elevation of [Ca2+]o, which explained the membrane depolarization caused by high [Ca2+]o. 4. Other divalent cations also inhibited the inwardly rectifying K+ current with the following order of potency: Ca2+ < Ni2+ < or = Co2+ < Cd2+. 5. In the presence of intracellular GTP gamma S the inwardly rectifying K+ current was irreversibly inhibited by [Ca2+]o, whereas the inhibition of the inwardly rectifying K+ current was greatly attenuated by intracellular application of GDP beta S. 6. Pertussis toxin (PTX) treatment did not abolish the inhibition of the inwardly rectifying K+ current caused by [Ca2+]o. 7. These results suggest that inwardly rectifying K+ channels in osteoclasts were regulated by a PTX-insensitive G-protein, which was coupled to the putative Ca2+ receptor or sensor on the cell membrane.