Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction

Kissaou T. Tchedre, Ren-Qi Huang, Adnan Dibas, Raghu Krishnamoorthy, Glenn H. Dillon, Thomas Yorio

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

PURPOSE. The σ-1 receptor belongs to a recently discovered family of transmembrane proteins expressed in the central nervous system, including the eye, and mediates the regulation of ion channels. The exact function of sigma receptors remains to be elucidated. The purpose of this study was to investigate the effect of σ-1 receptor ligands on calcium homeostasis in a retinal ganglion cell line (RGC)-5 and rat primary RGCs. METHODS. Calcium imaging was used to assess the effect of σ-1 receptor agonist (+)-N-allylnormetazocine ((+)-SKF10047) on potassium chloride (KCl)-induced calcium influx in RGC-5. The whole-cell patch clamp technique was used to analyze the effect of (+)-SKF10047 on calcium currents in primary RGCs. Coimmunoprecipitation assessed the interaction between the σ-1 receptor and the L-type voltage-gated calcium channel. RESULTS. The σ-1 receptor agonist (+)-SKF10047 inhibited potassium chloride (KCl)-induced calcium influx. The σ-1 receptor antagonist, BD1047, reversed the inhibitory effect of (+)-SKF10047. Whole-cell patch clamp recordings of rat cultured primary RGCs demonstrated that (+)-SKF10047 inhibited calcium currents. Coimmunoprecipitation studies demonstrated an association between L-type calcium channels and the σ-1 receptors. CONCLUSIONS. These results suggest that σ-1 receptor activation can regulate calcium homeostasis and signaling in RGCs, likely by directly influencing the activity of L-type voltage-gated calcium channels. Regulation of calcium influx in RGCs by σ-1 receptor ligands may represent in part the neuroprotective effect of σ-1 receptors.

Original languageEnglish
Pages (from-to)4993-5002
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number11
DOIs
StatePublished - 1 Nov 2008

Fingerprint

Calcium Channels
Calcium
Potassium Chloride
Retinal Ganglion Cells
Homeostasis
sigma Receptors
Ligands
Cell Line
L-Type Calcium Channels
Calcium Signaling
Neuroprotective Agents
Patch-Clamp Techniques
sigma-1 receptor
Ion Channels
Central Nervous System
Proteins

Cite this

@article{5acd341eb65c48828b0ec997fa0fcb5d,
title = "Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction",
abstract = "PURPOSE. The σ-1 receptor belongs to a recently discovered family of transmembrane proteins expressed in the central nervous system, including the eye, and mediates the regulation of ion channels. The exact function of sigma receptors remains to be elucidated. The purpose of this study was to investigate the effect of σ-1 receptor ligands on calcium homeostasis in a retinal ganglion cell line (RGC)-5 and rat primary RGCs. METHODS. Calcium imaging was used to assess the effect of σ-1 receptor agonist (+)-N-allylnormetazocine ((+)-SKF10047) on potassium chloride (KCl)-induced calcium influx in RGC-5. The whole-cell patch clamp technique was used to analyze the effect of (+)-SKF10047 on calcium currents in primary RGCs. Coimmunoprecipitation assessed the interaction between the σ-1 receptor and the L-type voltage-gated calcium channel. RESULTS. The σ-1 receptor agonist (+)-SKF10047 inhibited potassium chloride (KCl)-induced calcium influx. The σ-1 receptor antagonist, BD1047, reversed the inhibitory effect of (+)-SKF10047. Whole-cell patch clamp recordings of rat cultured primary RGCs demonstrated that (+)-SKF10047 inhibited calcium currents. Coimmunoprecipitation studies demonstrated an association between L-type calcium channels and the σ-1 receptors. CONCLUSIONS. These results suggest that σ-1 receptor activation can regulate calcium homeostasis and signaling in RGCs, likely by directly influencing the activity of L-type voltage-gated calcium channels. Regulation of calcium influx in RGCs by σ-1 receptor ligands may represent in part the neuroprotective effect of σ-1 receptors.",
author = "Tchedre, {Kissaou T.} and Ren-Qi Huang and Adnan Dibas and Raghu Krishnamoorthy and Dillon, {Glenn H.} and Thomas Yorio",
year = "2008",
month = "11",
day = "1",
doi = "10.1167/iovs.08-1867",
language = "English",
volume = "49",
pages = "4993--5002",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "11",

}

Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction. / Tchedre, Kissaou T.; Huang, Ren-Qi; Dibas, Adnan; Krishnamoorthy, Raghu; Dillon, Glenn H.; Yorio, Thomas.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 11, 01.11.2008, p. 4993-5002.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction

AU - Tchedre, Kissaou T.

AU - Huang, Ren-Qi

AU - Dibas, Adnan

AU - Krishnamoorthy, Raghu

AU - Dillon, Glenn H.

AU - Yorio, Thomas

PY - 2008/11/1

Y1 - 2008/11/1

N2 - PURPOSE. The σ-1 receptor belongs to a recently discovered family of transmembrane proteins expressed in the central nervous system, including the eye, and mediates the regulation of ion channels. The exact function of sigma receptors remains to be elucidated. The purpose of this study was to investigate the effect of σ-1 receptor ligands on calcium homeostasis in a retinal ganglion cell line (RGC)-5 and rat primary RGCs. METHODS. Calcium imaging was used to assess the effect of σ-1 receptor agonist (+)-N-allylnormetazocine ((+)-SKF10047) on potassium chloride (KCl)-induced calcium influx in RGC-5. The whole-cell patch clamp technique was used to analyze the effect of (+)-SKF10047 on calcium currents in primary RGCs. Coimmunoprecipitation assessed the interaction between the σ-1 receptor and the L-type voltage-gated calcium channel. RESULTS. The σ-1 receptor agonist (+)-SKF10047 inhibited potassium chloride (KCl)-induced calcium influx. The σ-1 receptor antagonist, BD1047, reversed the inhibitory effect of (+)-SKF10047. Whole-cell patch clamp recordings of rat cultured primary RGCs demonstrated that (+)-SKF10047 inhibited calcium currents. Coimmunoprecipitation studies demonstrated an association between L-type calcium channels and the σ-1 receptors. CONCLUSIONS. These results suggest that σ-1 receptor activation can regulate calcium homeostasis and signaling in RGCs, likely by directly influencing the activity of L-type voltage-gated calcium channels. Regulation of calcium influx in RGCs by σ-1 receptor ligands may represent in part the neuroprotective effect of σ-1 receptors.

AB - PURPOSE. The σ-1 receptor belongs to a recently discovered family of transmembrane proteins expressed in the central nervous system, including the eye, and mediates the regulation of ion channels. The exact function of sigma receptors remains to be elucidated. The purpose of this study was to investigate the effect of σ-1 receptor ligands on calcium homeostasis in a retinal ganglion cell line (RGC)-5 and rat primary RGCs. METHODS. Calcium imaging was used to assess the effect of σ-1 receptor agonist (+)-N-allylnormetazocine ((+)-SKF10047) on potassium chloride (KCl)-induced calcium influx in RGC-5. The whole-cell patch clamp technique was used to analyze the effect of (+)-SKF10047 on calcium currents in primary RGCs. Coimmunoprecipitation assessed the interaction between the σ-1 receptor and the L-type voltage-gated calcium channel. RESULTS. The σ-1 receptor agonist (+)-SKF10047 inhibited potassium chloride (KCl)-induced calcium influx. The σ-1 receptor antagonist, BD1047, reversed the inhibitory effect of (+)-SKF10047. Whole-cell patch clamp recordings of rat cultured primary RGCs demonstrated that (+)-SKF10047 inhibited calcium currents. Coimmunoprecipitation studies demonstrated an association between L-type calcium channels and the σ-1 receptors. CONCLUSIONS. These results suggest that σ-1 receptor activation can regulate calcium homeostasis and signaling in RGCs, likely by directly influencing the activity of L-type voltage-gated calcium channels. Regulation of calcium influx in RGCs by σ-1 receptor ligands may represent in part the neuroprotective effect of σ-1 receptors.

UR - http://www.scopus.com/inward/record.url?scp=56149083457&partnerID=8YFLogxK

U2 - 10.1167/iovs.08-1867

DO - 10.1167/iovs.08-1867

M3 - Article

C2 - 18641291

AN - SCOPUS:56149083457

VL - 49

SP - 4993

EP - 5002

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 11

ER -