Actions of the ORL1 receptor ligand nociceptin on membrane properties of rat periaqueductal gray neurons in vitro

Christopher W. Vaughan, Susan L. Ingram, MacDonald J. Christie

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

The actions of the endogenous ORL1-receptor ligand nociceptin on the membrane properties and synaptic currents in rat periaqueductal gray (PAG) neurons were examined by the use of whole-cell patch-clamp recording in brain slices. Nociceptin produced an outward current in all neurons tested, with an EC50 of 39 ± 7 nM. The outward current was unaffected by naloxone. Outward currents reversed polarity at 110 ± 3 mV in 2.5 mM extracellular potassium, and the reversal potential increased when the extracellular potassium concentration was raised (slope = 66.3 mV/log[K+](o) mM). Thus, the nociceptin-induced outward current was attributable to an increased K+ conductance. Nociceptin inhibited evoked fast GABAergic (IPSCs) and glutamatergic (EPSCs) postsynaptic currents and increased paired-pulse facilitation in a subpopulation of PAG neurons. Nociceptin inhibited evoked IPSCs and EPSCs in ~50% of neurons throughout the PAG, except in the ventrolateral PAG, where nociceptin inhibited evoked IPSCs in most neurons. Nociceptin decreased the frequency of spontaneous miniature postsynaptic currents (mIPSCs and mEPSCs) in a subpopulation of PAG neurons but had no effect on their amplitude distributions. Thus, nociceptin had a presynaptic inhibitory effect on transmitter release. These findings suggest that nociceptin, via its pre- and postsynaptic actions, has the potential to modulate the analgesic, behavioral, and autonomic functions of the PAG.

Original languageEnglish (US)
Pages (from-to)996-1003
Number of pages8
JournalJournal of Neuroscience
Volume17
Issue number3
DOIs
StatePublished - 1997

Keywords

  • ORL receptor
  • analgesia
  • nociceptin
  • opioid receptor
  • orphan receptor
  • periaqueductal gray
  • potassium channel
  • presynaptic inhibition

ASJC Scopus subject areas

  • Neuroscience(all)

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