Postsynaptic K+ current induced by nociceptin in medullary dorsal horn neurons.
The actions of the endogenous ORL1 receptor (opioid receptor-like1) ligand nociceptin on the membrane properties of rat trigeminal nucleus caudalis neurons were examined by use of whole cell and perforated patch clamp recording in brain slices. Nociceptin produced an outward current in all neurons tested (EC50 112 nM). The outward current produced by nociceptin was completely reversed with the addition of the non-peptide ORL1 antagonist J-113397. Outward currents reversed polarity at -99+/-2 mV, close to the potential for K+ of -102 mV, suggesting that they were mediated by an increased K+ conductance. These results suggest that the analgesic action of nociceptin might be mediated by direct postsynaptic inhibition within the dorsal horn.
Jennings
E A
EA
Department of Pharmacology, University of Sydney, NSW, Australia.
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology; D013376:Substantia Gelatinosa / Q000166:cytology / Q000502:physiology; D014275:Trigeminal Caudal Nucleus / Q000166:cytology / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000701:Analgesics, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018847:Opioid Peptides; D011188:Potassium; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C111148:nocistatin; C000722285:Oprl1 protein, rat