HIGH EXTRACELLULAR CA2-SENSING RECEPTOR AGONISTS ACTIVATE NONSELECTIVE CATION CONDUCTANCE IN FRESHLY ISOLATED RAT OSTEOCLASTS( AND CA2+)

The effects of an increase of extracellular and intracellular Ca2+ on the membrane properties were examined in freshly isolated rat osteocla sts using the perforated patch-clamp method. Spread-type osteoclasts p lated on a cover glass predominantly displayed an inwardly rectifying K+ current in a normal saline solution. Application of an extracellula r high-Ca2+ solution transiently increased the membrane conductance in 15 (71%) of 21 osteoclasts. The external high Ca2+- induced current r eversed at the membrane potential of -4.8 +/- 2.4 mV (n = 8), The chan ge of intracellular Cl- concentration did not affect the reversal pote ntial, suggesting that the response was due to a nonselective cation c onductance, Application of a calcium ionophore, ionomycin (3 mu mol/L) , continuously increased the membrane conductance, and the reversal po tential was -12.5 +/- 5.0 mV (n = 5), Extracellularly applied neomycin (100 mu mol/L) and Gd3+ (100 mu mol/L), which are agonists of Ca2+-se nsing receptor (CaR), also increased the membrane conductance, These r esults suggest that rat osteoclasts detect high extracellular Ca2+ by an extracellular Ca2+-sensing mechanism functionally similar to the Ca R in the cell surface, release Ca2+ from the internal stores, and disp lay the activation of Ca2+-dependent cation channels in the cell membr ane. (C) 1998 by Elsevier Science Inc. All rights reserved.