Distinct inhibition of voltage-activated Ca2+ channels by δ-opioid agonists in dorsal root ganglion neurons devoid of functional T-type Ca2+ currents

Z. Z. Wu, S. R. Chen, H. L. Pan

Research output: Contribution to journalArticlepeer-review

Abstract

Both μ- and δ-opioid agonists selectively inhibit nociception but have little effect on other sensory modalities. Voltage-activated Ca2+ channels in the primary sensory neurons are important for the regulation of nociceptive transmission. In this study, we determined the effect of δ-opioid agonists on voltage-activated Ca2+ channel currents (ICa) in small-diameter rat dorsal root ganglion (DRG) neurons that do and do not bind isolectin B4 (IB4). The δ-opioid agonists [d-Pen2,d-Pen5]-enkephalin (DPDPE) and deltorphin II produced a greater inhibition of high voltage-activated ICa in IB4-negative than IB4-positive neurons. Furthermore, DPDPE produced a greater inhibition of N-, P/Q-, and L-type ICa in IB4-negative than IB4-positive neurons. However, DPDPE had no significant effect on the R-type ICa in either type of cells. We were surprised to find that DPDPE failed to inhibit either the T-type or high voltage-activated ICa in all the DRG neurons with T-type ICa. Double immunofluorescence labeling showed that the majority of the δ-opioid receptor-immunoreactive DRG neurons had IB4 labeling, while all DRG neurons immunoreactive to δ-opioid receptors exhibited Cav3.2 immunoreactivity. Additionally, DPDPE significantly inhibited high voltage-activated ICa in Tyrode's or N-methyl-d-glucamine solution but not in tetraethylammonium solution. This study provides new information that δ-opioid agonists have a distinct effect on voltage-activated Ca2+ channels in different phenotypes of primary sensory neurons. High voltage-activated Ca2+ channels are more sensitive to inhibition by δ-opioid agonists in IB4-negative than IB4-positive neurons, and this opioid effect is restricted to DRG neurons devoid of functional T-type Ca2+ currents.

Original languageEnglish (US)
Pages (from-to)1256-1267
Number of pages12
JournalNeuroscience
Volume153
Issue number4
DOIs
StatePublished - Jun 2 2008
Externally publishedYes

Keywords

  • T-type calcium channels
  • analgesia
  • dorsal root ganglia
  • nociceptors
  • opioid receptors
  • tetraethylammonium

ASJC Scopus subject areas

  • Neuroscience(all)

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