Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Keywords: calcium • signal transduction • ganglion cells