May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Sigma-1 Receptor Regulation of Voltage-Gated Calcium Channels Involves a Direct Interaction Between Sigma-1 Receptor and Voltage-Gated L-Type Calcium Channel
Author Affiliations & Notes
  • K. T. Tchedre
    University of North Texas Hlth Sci Ctr, Fort Worth, Texas
    Biomedical Sciences,
  • R.-Q. Huang
    University of North Texas Hlth Sci Ctr, Fort Worth, Texas
    Pharmacology& Neurosciences,
  • A. Dibas
    University of North Texas Hlth Sci Ctr, Fort Worth, Texas
    Pharmacology& Neurosciences,
  • R. R. Krishnamoorthy
    University of North Texas Hlth Sci Ctr, Fort Worth, Texas
    Pharmacology& Neurosciences,
  • G. H. Dillon
    University of North Texas Hlth Sci Ctr, Fort Worth, Texas
    Pharmacology& Neurosciences,
  • T. Yorio
    University of North Texas Hlth Sci Ctr, Fort Worth, Texas
    Pharmacology& Neurosciences,
  • Footnotes
    Commercial Relationships  K.T. Tchedre, None; R. Huang, None; A. Dibas, None; R.R. Krishnamoorthy, None; G.H. Dillon, None; T. Yorio, None.
  • Footnotes
    Support  Texas Higher Education Coordinator Board and a NSF SCORE (Schools' Cooperative Opportunities for Resources) training grant.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2062. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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