Actions of the ORL1 receptor ligand nociceptin on membrane properties of rat periaqueductal gray neurons in vitro.
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 (IP-SCs) and glutamatergic (EPSCs) postsynaptic currents and increased paired-pulse facilitation in a subpopulation of PAG neurons. Nociceptin inhibited evoked IPSCs and EPSCs in approximately 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.
Vaughan
C W
CW
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Ingram
S L
SL
Christie
M J
MJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000166:cytology / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000819:agonists*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D000097629:Nociceptin
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D018847:Opioid Peptides; D011188:Potassium; D018079:Receptors, GABA; D011957:Receptors, Opioid; D017661:Receptors, Presynaptic; D013779:Tetrodotoxin; D000097629:Nociceptin