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

Kajiya, Hiroshi, Fujio Okamoto, Hidefumi Fukushima, Keisuke Takada, and Koji Okabe. Mechanism and role of high-potassium-induced reduction of intracellular Ca2 concentration in rat osteoclasts. Am J Physiol Cell Physiol 285: C457–C466, 2003. First published April 9, 2003; 10.1152/ajpcell.00033.2003.—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 M 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 Land 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.