Sigma-1 receptors do not regulate calcium influx through voltage-dependent calcium channels in mouse brain synaptosomes.
Several lines of evidence suggest that σ(1) receptors regulate intracellular calcium concentration [Ca(2+)](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 [Ca(2+)](i) under basal conditions and after depolarization with KCl in fura-2-loaded synaptosomes from wild-type and σ(1) receptor knockout (σ(1)R-KO) mice. We also tested the effects of the selective σ(1) receptor agonists PRE-084 and (+)-pentazocine and antagonists BD-1047 and NE-100 on the increase in [Ca(2+)](i) induced by depolarization with 60mM KCl. Mibefradil, a nonselective blocker of VDCCs, was used as a positive control. Basal [Ca(2+)](i) and the increase in [Ca(2+)](i) caused by KCl-induced depolarization were similar in brain synaptosomes from both wild-type and σ(1)R-KO mice. Mibefradil (1-30 μM) and all σ(1) receptor ligands studied (3-100 μM) inhibited the KCl-induced increase in [Ca(2+)](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 σ(1)R-KO mice. These findings indicate that σ(1) receptors are not involved in calcium influx through VDCCs or in the inhibitory effects of these σ(1) ligands on Ca(2+) channels.
Department of Pharmacology and Neurosciences Institute, Faculty of Medicine, University of Granada, Avenida de Madrid 11, E-18012 Granada, Spain.
Luis G
LG
González
Cristina
C
Sánchez-Fernández
Enrique J
EJ
Cobos
José M
JM
Baeyens
Esperanza
E
del Pozo
D000818:Animals; D001921:Brain / Q000166:cytology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D055786:Gene Knockout Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D011189:Potassium Chloride / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D000097605:Sigma-1 Receptor
D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011189:Potassium Chloride; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor