title: Mechanism and role of high-potassium-induced reduction of intracellular Ca2+ concentration in rat osteoclasts.
abstract: 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 microM La3+ reduced [Ca2+]i to approximately 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.
authors.affiliation: Department of Physiological Science and Molecular Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan. kajiya@college.fdcnet.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiya
authors.forename: Fujio
authors.initials: F
authors.lastname: Okamoto
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Fukushima
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takada
authors.forename: Koji
authors.initials: K
authors.lastname: Okabe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002121:Calcium Channel Blockers; D007811:Lanthanum; D011188:Potassium; D002118:Calcium