PT  - JOURNAL ARTICLE
AU  - Pan, Bin
AU  - Guo, Yuan
AU  - Kwok, Wai-Meng
AU  - Hogan, Quinn
AU  - Wu, Hsiang-en
TI  - Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca<sup>2+</sup> Current in Sensory Neurons
AID  - 10.1124/jpet.114.214320
DP  - 2014 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 290--300
VI  - 350
IP  - 2
4099  - http://jpet.aspetjournals.org/content/350/2/290.short
4100  - http://jpet.aspetjournals.org/content/350/2/290.full
SO  - J Pharmacol Exp Ther2014 Aug 01; 350
AB  - 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 (ICa) with Ba2+ as charge carrier in control sensory neurons. The inhibitory effect of σ1R agonists on ICa was blocked by σ1R antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-m​ethylpiperazine dihydrochloride) or BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-m​ethyl-2-(dimethylamino)ethylamine dihydrobromide). PTZ and DTG showed similar effect on ICa 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 ICa 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 ICa in sensory neurons and may play a pivotal role in pain generation.