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K. T. Tchedre, R.-Q. Huang, A. Dibas, R. R. Krishnamoorthy, G. H. Dillon, T. Yorio; Sigma-1 Receptor Regulation of Voltage-Gated Calcium Channels Involves a Direct Interaction Between Sigma-1 Receptor and Voltage-Gated L-Type Calcium Channel. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2062.
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© ARVO (1962-2015); The Authors (2016-present)
The sigma-1 receptor is a recently discovered transmembrane protein that mediates the regulation of ion channels. Although the sigma-1 receptor was cloned almost a decade ago, the exact function of sigma receptors in the eye remains to be elucidated. The purpose of this study was to investigate the effect of sigma-1 receptor ligands on the intracellular calcium levels in a retinal ganglion cell line (RGC-5), and rat primary retinal ganglion cells.
Calcium imaging was used to assess the effect of sigma-1 receptor agonist (+)-N-allylnormetazocine ((+)-SKF10047) effect on potassium chloride (KCl)-induced calcium influx in RGC-5 cells. The whole cell patch clamp technique was used to analyze the effect of sigma-1 receptor ligand (+)-SKF10047 on calcium currents in primary retinal ganglion cells. The co-immunoprecipitation was used assess the interaction between sigma-1 receptor and voltage gated L-type calcium channel.
Our studies showed that the sigma-1 receptor agonist (+)-N-allylnormetazocine ((+)-SKF10047) inhibits potassium chloride (KCl)-induced calcium influx. The sigma-1 receptor antagonist, [2-(3,4-dichlorophenyl) ethyl]-N-methyl-2- (diamino) ethylamine (BD1047) reversed the inhibitory effect of (+)-SKF10047. Using the co-immunoprecipitation technique, we reported for the first time the association between L-type calcium channels and sigma-1 receptors. Thus sigma-1 receptor ligands may indirectly influence the voltage-gated calcium channels by interacting with the sigma-1 receptor associated voltage-gated calcium channel complex. In addition, the whole-cell patch clamp of rat cultured primary retinal ganglion cells demonstrated that sigma-1 receptor agonist (+)-SKF10047 inhibits calcium channel currents.
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