Ion channels and transporters in osteoclasts.

The resorbing osteoclast is an exceptional cell that secretes large amounts of acid through the coupled activity of a v-type H+-ATPase and a chloride channel that both reside in the ruffled membrane. Impairment of this acid secretion machinery by genetic mutations can abolish bone resorption activity, resulting in osteopetrotic phenotypes. Another key feature of osteoclasts is the transport of high amounts of calcium and phosphate from the resorption lacuna to the basolateral plasma membrane. Evidence exists that this occurs in part through entry of these ions into the osteoclast cytosol. Handling of such large amounts of a cellular messenger requires elaborate mechanisms. Membrane proteins that regulate osteoclast calcium homeostasis and the effect of calcium on osteoclast function and survival are therefore the second main focus of this review.