Sigma-1 receptor antagonism restores injury-induced decrease of voltage-gated Ca2+ current in sensory neurons

Bin Pan, Yuan Guo, Wai Meng Kwok, Quinn Hogan, Hsiang En Wu

Research output: Contribution to journalArticlepeer-review

Abstract

Sigma-1 receptor (σ1R), an endoplasmic reticulum-chaperone protein, can modulate painful response after peripheral nerve injury. We have demonstrated that voltage-gated calcium current is inhibited in axotomized sensory neurons. We examined whether σ1R contributes to the sensory dysfunction of voltage-gated calcium channel (VGCC) after peripheral nerve injury through electrophysiological approach in dissociated rat dorsal root ganglion (DRG) neurons. Animals received either skin incision (Control) or spinal nerve ligation (SNL). Both σ1R agonists, (+)pentazocine (PTZ) and DTG [1,3-di-(2-tolyl)guanidine], dose dependently inhibited calcium current (/Ca) with Ba2+ as charge carrier in control sensory neurons. The inhibitory effect of σ1R agonists on/Ca was blocked by s1R antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4- methylpiperazine dihydrochloride) or BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N- methyl-2-(dimethylamino)ethylamine dihydrobromide). PTZ and DTG showed similar effect on/Ca in axotomized fifth DRG neurons (SNL L5). Both PTZ and DTG shifted the voltage-dependent activation and steady-state inactivation of VGCC to the left and accelerated VGCC inactivation rate in both Control and axotomized L5 SNL DRG neurons. The σ1R antagonist, BD1063 (10 μM), increases/Ca in SNL L5 neurons but had no effect on Control and noninjured fourth lumbar neurons in SNL rats. Together, the findings suggest that activation of σR1 decreases/Ca in sensory neurons and may play a pivotal role in pain generation.

Original languageEnglish (US)
Pages (from-to)290-300
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume350
Issue number2
DOIs
StatePublished - Aug 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint

Dive into the research topics of 'Sigma-1 receptor antagonism restores injury-induced decrease of voltage-gated Ca2+ current in sensory neurons'. Together they form a unique fingerprint.

Cite this