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Volume 17, Number 3, Issue of February 1, 1997 pp. 996-1003
Copyright ©1997 Society for NeuroscienceActions of the ORL1 Receptor Ligand Nociceptin on Membrane Properties of Rat Periaqueductal Gray Neurons In Vitro
Received Sept. 30, 1996; revised Nov. 13, 1996; accepted Nov. 15, 1996.
Christopher W. Vaughan1, 2, Susan L. Ingram1, and MacDonald J. Christie1 Departments of 1 Pharmacology and 2 Anatomy and Histology, University of Sydney, New South Wales 2006, Australia
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.
Key words: orphan receptor; ORL1 receptor; opioid receptor; nociceptin; potassium channel; presynaptic inhibition; periaqueductal gray; analgesia
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