Mechanism and role of high-potassium-induced reduction of intracellular Ca[sup 2+] 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 Ca[sup 2+] concentration ([Ca[sup 2+]][sub i]) in nonresorbing vs. resorbing rat osteoclasts. Basal [Ca[sup 2+]][sub 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[sup +] reduced [Ca[sup 2+]][sub i], whereas high K[sup +] increased [Ca[sup 2+]][sub i] in resorbing state osteoclasts. In nonresorbing/motile ceils, membrane depolarization and hyperpolarization appiled by the patch-clamp technique decreased and increased [Ca[sup 2+]][sub i], respectively. Removal of extracellular Ca[sup 2+] or application of 300 µM La[sup 3+] reduced [Ca[sup 2+][sub i] to ∼50 nM in nonresorbing/motile osteoclasts, and high-K[sup +]-induced reduction of [Ca[sup 2+]][sub i] could not be observed under these conditions. Neither inhibition of intracellular Ca[sup 2+] stores or plasma membrane Ca[sup 2+] pumps nor blocking of L- and N-type Ca[sup 2+] channels significantly reduced [Ca[sup 2+][sub i]. Exposure to high K[sup +] 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 La[sup 3+]-sensitive Ca[sup 2+] entry pathway is continuously active under resting conditions, keeping [Ca[sup 2+]][sub i] high. Changes in membrane potential regulate osteoclastic motility by controlling the net amount of Ca[sup 2+] entry in a "reversed" voltage-dependent manner, i.e., depolarization decreases and hyperpolarization increases [Ca[sup 2+]][sub i]. [ABSTRACT FROM AUTHOR]