Mechanism and role of high-potassium-induced reduction of intracellular Ca2+ concentration in rat osteoclasts

Osteoclasts are multinucleated, bone-resorbing cells that show structural and functional differences between the resorbing and nonresorbing (motile) states during the bone resorption cycle. In the present study, we measured intracellular Ca²⁺ concentration ([Ca²⁺]_i) in nonresorbing vs. resorbing rat osteoclasts. Basal [Ca²⁺]_i in osteoclasts possessing pseudopodia (nonresorbing/motile state) was around 110 nM and significantly higher than that in actin ring-forming osteoclasts (resorbing state, around 50 nM). In nonresorbing/motile osteoclasts, exposure to high K⁺ reduced [Ca²⁺]_i, whereas high K⁺ increased [Ca²⁺]_i in resorbing state osteoclasts. In nonresorbing/motile cells, membrane depolarization and hyperpolarization applied by the patch-clamp technique decreased and increased [Ca²⁺]_i, respectively. Removal of extracellular Ca²⁺ or application of 300 µM La³⁺ reduced [Ca²⁺]_i to 50 nM in nonresorbing/motile osteoclasts, and high-K⁺-induced reduction of [Ca²⁺]_i could not be observed under these conditions. Neither inhibition of intracellular Ca²⁺ stores or plasma membrane Ca²⁺ pumps nor blocking of L- and N-type Ca²⁺ channels significantly reduced [Ca²⁺]_i. Exposure to high K⁺ inhibited the motility of nonresorbing osteoclasts and reduced the number of actin rings and pit formation in resorbing osteoclasts. These results indicate that in nonresorbing/motile osteoclasts, a La³⁺-sensitive Ca²⁺ entry pathway is continuously active under resting conditions, keeping [Ca²⁺]_i high. Changes in membrane potential regulate osteoclastic motility by controlling the net amount of Ca²⁺ entry in a "reversed" voltage-dependent manner, i.e., depolarization decreases and hyperpolarization increases [Ca²⁺]_i. membrane depolarization; resorbing and motile activities; bone resorbing cycle