کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6197314 | 1602615 | 2013 | 11 صفحه PDF | دانلود رایگان |
Sigma-1 receptors (Ï-1rs) exert neuroprotective effects on retinal ganglion cells (RGCs) both in vivo and in vitro. This receptor has unique properties through its actions on several voltage-gated and ligand-gated channels. The purpose of this study was to investigate the role that Ï-1rs play in regulating cell calcium dynamics through activated L-type Voltage Gated Calcium Channels (L-type VGCCs) in purified RGCs. RGCs were isolated from P3-P7 Sprague-Dawley rats and purified by sequential immunopanning using a Thy1.1 antibody. Calcium imaging was used to measure changes in intracellular calcium after depolarizing the cells with potassium chloride (KCl) in the presence or absence of two Ï-1r agonists [(+)-SKF10047 and (+)-Pentazocine], one Ï-1r antagonist (BD1047), and one L-type VGCC antagonist (Verapamil). Finally, co-localization studies were completed to assess the proximity of Ï-1r with L-type VGCCs in purified RGCs. VGCCs were activated using KCl (20 mM). Pre-treatment with a known L-type VGCC blocker demonstrated a 57% decrease of calcium ion influx through activated VGCCs. Calcium imaging results also demonstrated that Ï-1r agonists, (+)-N-allylnormetazocine hydrochloride [(+)-SKF10047] and (+)-Pentazocine, inhibited calcium ion influx through activated VGCCs. Antagonist treatment using BD1047 demonstrated a potentiation of calcium ion influx through activated VGCCs and abolished all inhibitory effects of the Ï-1r agonists on VGCCs, implying that these ligands were acting through the Ï-1r. An L-type VGCC blocker (Verapamil) also inhibited KCl activated VGCCs and when combined with the Ï-1r agonists there was not a further decline in calcium entry suggesting similar mechanisms. Lastly, co-localization studies demonstrated that Ï-1rs and L-type VGCCs are co-localized in purified RGCs. Taken together, these results indicated that Ï-1r agonists can inhibit KCl induced calcium ion influx through activated L-type VGCCs in purified RGCs. This is the first report of attenuation of L-type VGCC signaling through the activation of Ï-1rs in purified RGCs. The ability of Ï-1rs to co-localize with L-type VGCCs in purified RGCs implied that these two proteins are in close proximity to each other and that such interactions regulate L-type VGCCs.
⺠Sigma-1 receptor ligands decrease calcium ion influx through ion and voltage gated channels. ⺠Sigma-1 receptor ligands decrease calcium ion influx through calcium channels. ⺠Sigma-1 receptors block only the L-type Voltage Gated Calcium Channels. ⺠Actions on calcium influx protect retinal ganglion cells from cell death during stress.
Journal: Experimental Eye Research - Volume 107, February 2013, Pages 21-31