Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil

Mone Zaidi; Iain MacIntyre; Harish Datta

doi:10.1016/0006-291X(90)92097-J

Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil

Mone Zaidi, Iain MacIntyre, Harish Datta

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Abstract

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 μM 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.

Original language	English
Pages (from-to)	807-812
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	167
Issue number	2
DOIs	https://doi.org/10.1016/0006-291X(90)92097-J
State	Published - 16 Mar 1990
Externally published	Yes

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title = "Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil",

abstract = "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 μM 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.",

author = "Mone Zaidi and Iain MacIntyre and Harish Datta",

note = "Funding Information: Acknowledements; These studies were supported by grants from The Arthritis and Rheumatism Council, UK (MZ), Research into Ageing, UK (MZ), Leverhulme Trust, UK (MZ) and Bartos Foundation, USA (IM). HKD acknowledges the support of The Medical Research Council, UK.",

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doi = "10.1016/0006-291X(90)92097-J",

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T1 - Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil

AU - Zaidi, Mone

AU - MacIntyre, Iain

AU - Datta, Harish

N1 - Funding Information: Acknowledements; These studies were supported by grants from The Arthritis and Rheumatism Council, UK (MZ), Research into Ageing, UK (MZ), Leverhulme Trust, UK (MZ) and Bartos Foundation, USA (IM). HKD acknowledges the support of The Medical Research Council, UK.

PY - 1990/3/16

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N2 - 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 μM 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.

AB - 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 μM 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.

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Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil

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