Opioid receptors modulate diverse types of calcium channels in the nucleus tractus solitarius of the rat

Hyewhon Rhim, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


We have investigated the coupling between opioid receptors and different types of Ca2+ channels in neurons acutely isolated from the nucleus tractus solitarius (NTS) of the rat. Using fura-2-based imaging we found that Ca2+ transients evoked by depolarization with 50 mM KCl were suppressed by the μ- opioid receptor agonist D-Ala2,N-MePhe4,Gly5-ol-enkephalin (DAMGO) and less effectively by the κ-receptor agonist U-69,593. The δ-receptor agonist D-Pen2,D-Pen5-enkephalin (DPDPE) was ineffective. In whole-cell voltage- clamp recordings from these neurons, depolarizing voltage steps elicited high-threshold Ca2+ currents that could be distinguished pharmacologically into different components. Part of the current could be blocked by dihydropyridines, part by ω-conotoxin-GVIA and part by ω-agatoxin-IVA. This suggests that the neurons contained L-, N-, and P/Q-type Ca2+ channels. DAMGO and U-69,593 both blocked part of the Ca2+ current but DPDPE was ineffective. Perfusion of GTP-γ-S into the cells produced a rapid rundown of the Ca2+ current and occluded further effects of the opioid agonists, suggesting the involvement of a G-protein in the coupling mechanism. Inhibition of L-channels did not alter the effect of DAMGO. On the other hand inhibition of N-channels occluded about 80% of the effect of DAMGO. Inhibition of the P/Q-current occluded the remainder of the DAMGO effect. Thus, it appears that activation of opioid receptors can inhibit N- and P/Q- type Ca2+ channels but not L-channels in these cells. It is likely that such effects are important in opioid-mediated inhibition of transmitter release in the brain.

Original languageEnglish (US)
Pages (from-to)7608-7615
Number of pages8
JournalJournal of Neuroscience
Issue number12
StatePublished - 1994


  • autonomic nervous system
  • dihydropyridine
  • enkephalin
  • μ-opioid receptor
  • ω-agatoxin-IVA
  • ω-conotoxin- GVIA

ASJC Scopus subject areas

  • Neuroscience(all)

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