Sigma-1 receptors do not regulate calcium influx through voltage-dependent calcium channels in mouse brain synaptosomes

Several lines of evidence suggest that σ1 receptors regulate intracellular calcium concentration [Ca2+]i. However, no previous studies have demonstrated a consistent role for these receptors in the modulation of extracellular calcium entry through plasmalemmal voltage-dependent calcium channels (VDC...

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Bibliographic Details
Published in:European journal of pharmacology 2012-02, Vol.677 (1-3), p.102-106
Main Authors: González, Luis G., Sánchez-Fernández, Cristina, Cobos, Enrique J., Baeyens, José M., del Pozo, Esperanza
Format: Article
Language:English
Subjects:
agonists
Animals
Antagonists
Brain
Brain - cytology
calcium
Calcium (extracellular)
Calcium (intracellular)
Calcium - metabolism
Calcium Channel Blockers - pharmacology
calcium channels
Calcium channels (voltage-gated)
Calcium Channels - metabolism
Calcium influx
Fura-2/AM
Gene Knockout Techniques
Intracellular calcium concentration
Knockout mice
Membrane Potentials - drug effects
Mice
pharmacology
potassium chloride
Potassium Chloride - pharmacology
receptors
Receptors, sigma - agonists
Receptors, sigma - antagonists & inhibitors
Receptors, sigma - deficiency
Receptors, sigma - metabolism
Serotonin S1 receptors
Sigma-1 Receptor
Synaptosome
Synaptosomes
Synaptosomes - drug effects
Synaptosomes - metabolism
Voltage-dependent calcium channel
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Summary:Several lines of evidence suggest that σ1 receptors regulate intracellular calcium concentration [Ca2+]i. However, no previous studies have demonstrated a consistent role for these receptors in the modulation of extracellular calcium entry through plasmalemmal voltage-dependent calcium channels (VDCCs). To search for evidence of such a role we compared [Ca2+]i under basal conditions and after depolarization with KCl in fura-2-loaded synaptosomes from wild-type and σ1 receptor knockout (σ1R-KO) mice. We also tested the effects of the selective σ1 receptor agonists PRE-084 and (+)-pentazocine and antagonists BD-1047 and NE-100 on the increase in [Ca2+]i induced by depolarization with 60mM KCl. Mibefradil, a nonselective blocker of VDCCs, was used as a positive control. Basal [Ca2+]i and the increase in [Ca2+]i caused by KCl-induced depolarization were similar in brain synaptosomes from both wild-type and σ1R-KO mice. Mibefradil (1–30μM) and all σ1 receptor ligands studied (3–100μM) inhibited the KCl-induced increase in [Ca2+]i in a concentration-dependent way. The order of maximum inhibition for the ligands compared here was NE-100>BD-1047=PRE 084>(+)-pentazocine. There were no appreciable differences in their effects between wild-type and σ1R-KO mice. These findings indicate that σ1 receptors are not involved in calcium influx through VDCCs or in the inhibitory effects of these σ1 ligands on Ca2+ channels.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2011.12.029