Active NMDA glutamate receptors are expressed by mammalian osteoclasts

L Espinosa, Cecile Itzstein, H Cheynel, P D Delmas, C Chenu

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

1. The N-methyl-D-aspartate (NMDA) glutamate receptor, widely distributed in the mammalian nervous system, has recently been identified in bone. In this study, we have investigated whether NMDA receptors expressed by osteoclasts have an electrophysiological activity. 2. Using the patch clamp technique two agonists of the NMDA receptor, L-glutamate (Glu) and NMDA, were shown to activate whole-cell currents recorded in isolated rabbit osteoclasts. 3. The current-voltage (I-V ) relationships of the currents induced by Glu (IGlu) and NMDA (INMDA) were studied using Mg2+-free solutions. The agonist-induced currents had a linear I-V relationship with a reversal potential near 0 mV, as expected for a voltage independent and non-selective cationic current. 4. IGlu and INMDA were sensitive to specific blockers of NMDA subtype glutamate receptors, such as magnesium ions, (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten -5,10-imine (MK-801) and 1-(1,2-diphenylethyl) piperidine (DEP). The block of IGlu and INMDA by these specific antagonists was voltage dependent, strong for negative potentials (inward current) and absent for positive potentials (outward current). 5. These results demonstrate that NMDA receptors are functional in rabbit osteoclasts, and that their electrophysiological and pharmacological properties in these cells are similar to those documented for neuronal cells. Active NMDA receptors expressed by osteoclasts may represent a new target for regulating bone resorption.
Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalThe Journal of Physiology
Volume518 ( Pt 1)
Publication statusPublished - 1 Jul 1999

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Glutamate Receptors
Osteoclasts
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Rabbits
Imines
Dizocilpine Maleate
Patch-Clamp Techniques
Bone Resorption
Magnesium
Nervous System
Glutamic Acid
N-methylglutamate
Pharmacology
Ions
Bone and Bones

Keywords

  • Animals
  • Bone Remodeling
  • Dizocilpine Maleate
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Amino Acid Agonists
  • Glutamic Acid
  • Kinetics
  • Membrane Potentials
  • N-Methylaspartate
  • Osteoclasts
  • Patch-Clamp Techniques
  • Rabbits
  • Receptors, N-Methyl-D-Aspartate

Cite this

Espinosa, L., Itzstein, C., Cheynel, H., Delmas, P. D., & Chenu, C. (1999). Active NMDA glutamate receptors are expressed by mammalian osteoclasts. The Journal of Physiology, 518 ( Pt 1), 47-53.

Active NMDA glutamate receptors are expressed by mammalian osteoclasts. / Espinosa, L; Itzstein, Cecile; Cheynel, H; Delmas, P D; Chenu, C.

In: The Journal of Physiology, Vol. 518 ( Pt 1), 01.07.1999, p. 47-53.

Research output: Contribution to journalArticle

Espinosa, L, Itzstein, C, Cheynel, H, Delmas, PD & Chenu, C 1999, 'Active NMDA glutamate receptors are expressed by mammalian osteoclasts', The Journal of Physiology, vol. 518 ( Pt 1), pp. 47-53.
Espinosa L, Itzstein C, Cheynel H, Delmas PD, Chenu C. Active NMDA glutamate receptors are expressed by mammalian osteoclasts. The Journal of Physiology. 1999 Jul 1;518 ( Pt 1):47-53.
Espinosa, L ; Itzstein, Cecile ; Cheynel, H ; Delmas, P D ; Chenu, C. / Active NMDA glutamate receptors are expressed by mammalian osteoclasts. In: The Journal of Physiology. 1999 ; Vol. 518 ( Pt 1). pp. 47-53.
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AU - Itzstein, Cecile

AU - Cheynel, H

AU - Delmas, P D

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N2 - 1. The N-methyl-D-aspartate (NMDA) glutamate receptor, widely distributed in the mammalian nervous system, has recently been identified in bone. In this study, we have investigated whether NMDA receptors expressed by osteoclasts have an electrophysiological activity. 2. Using the patch clamp technique two agonists of the NMDA receptor, L-glutamate (Glu) and NMDA, were shown to activate whole-cell currents recorded in isolated rabbit osteoclasts. 3. The current-voltage (I-V ) relationships of the currents induced by Glu (IGlu) and NMDA (INMDA) were studied using Mg2+-free solutions. The agonist-induced currents had a linear I-V relationship with a reversal potential near 0 mV, as expected for a voltage independent and non-selective cationic current. 4. IGlu and INMDA were sensitive to specific blockers of NMDA subtype glutamate receptors, such as magnesium ions, (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten -5,10-imine (MK-801) and 1-(1,2-diphenylethyl) piperidine (DEP). The block of IGlu and INMDA by these specific antagonists was voltage dependent, strong for negative potentials (inward current) and absent for positive potentials (outward current). 5. These results demonstrate that NMDA receptors are functional in rabbit osteoclasts, and that their electrophysiological and pharmacological properties in these cells are similar to those documented for neuronal cells. Active NMDA receptors expressed by osteoclasts may represent a new target for regulating bone resorption.

AB - 1. The N-methyl-D-aspartate (NMDA) glutamate receptor, widely distributed in the mammalian nervous system, has recently been identified in bone. In this study, we have investigated whether NMDA receptors expressed by osteoclasts have an electrophysiological activity. 2. Using the patch clamp technique two agonists of the NMDA receptor, L-glutamate (Glu) and NMDA, were shown to activate whole-cell currents recorded in isolated rabbit osteoclasts. 3. The current-voltage (I-V ) relationships of the currents induced by Glu (IGlu) and NMDA (INMDA) were studied using Mg2+-free solutions. The agonist-induced currents had a linear I-V relationship with a reversal potential near 0 mV, as expected for a voltage independent and non-selective cationic current. 4. IGlu and INMDA were sensitive to specific blockers of NMDA subtype glutamate receptors, such as magnesium ions, (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten -5,10-imine (MK-801) and 1-(1,2-diphenylethyl) piperidine (DEP). The block of IGlu and INMDA by these specific antagonists was voltage dependent, strong for negative potentials (inward current) and absent for positive potentials (outward current). 5. These results demonstrate that NMDA receptors are functional in rabbit osteoclasts, and that their electrophysiological and pharmacological properties in these cells are similar to those documented for neuronal cells. Active NMDA receptors expressed by osteoclasts may represent a new target for regulating bone resorption.

KW - Animals

KW - Bone Remodeling

KW - Dizocilpine Maleate

KW - Electric Stimulation

KW - Electrophysiology

KW - Excitatory Amino Acid Agonists

KW - Glutamic Acid

KW - Kinetics

KW - Membrane Potentials

KW - N-Methylaspartate

KW - Osteoclasts

KW - Patch-Clamp Techniques

KW - Rabbits

KW - Receptors, N-Methyl-D-Aspartate

M3 - Article

VL - 518 ( Pt 1)

SP - 47

EP - 53

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

ER -