Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil.
We report here for the first time that verapamil elevates cytosolic calcium. We have found that in the isolated rat osteoclast, verapamil at low micromolar concentrations did not block the elevation of cytosolic free calcium ([Ca++]i) in response to elevated extracellular calcium concentrations ([Ca++]e). However, high micromolar concentrations of verapamil (300 microM or above) led to a rapid sustained elevation of [Ca++]i. These concentrations of verapamil had effects on osteoclast morphology and resorptive activity that were similar to those produced by elevated [Ca++]e: there was a marked dose-dependent fall in cell spread area and osteoclastic bone resorption. The sensitivity of osteoclasts to high micromolar concentrations of verapamil is unique and could not be mimicked in macrophages and lymphocytes.
Zaidi
M
M
Cell Biology Unit, Royal Postgraduate Medical School, London, UK.
MacIntyre
I
I
Datta
H
H
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D007211:Indoles; D007700:Kinetics; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014700:Verapamil / Q000494:pharmacology*
D005456:Fluorescent Dyes; D007211:Indoles; C059587:Indo-1 pentaacetoxymethyl ester; D014700:Verapamil; D002118:Calcium