INCREASE BY THE ORL(1) RECEPTOR (OPIOID RECEPTOR-LIKE(1)) LIGAND, NOCICEPTIN, OF INWARDLY RECTIFYING K CONDUCTANCE IN DORSAL RAPHE NUCLEUS NEURONS

The actions of the endogenous ORL(1)-receptor (opioid receptor-like(1) ) ligand, nociceptin, on the membrane properties of rat dorsal raphe n ucleus neurones were examined by use of whole-cell patch clamp recordi ng in brain slices. Nociceptin produced an outward current in all neur ones tested, with an EC(50) of 12+/-2 nM. Dynorphin A (100 nM to 1 mu M) produced little outward current. Outward currents reversed polarity near the predicted K+ equilibrium potential in both 2.5 mM (measured/ predicted = -105 mV/-104 mV) and 6.5 mM (measured/predicted = -80 mV/- 77 mV) extracellular K+. The conductance increase was larger between - 120 and -130 mV than between -70 and -80 mV, demonstrating that the no ciceptin-induced K current was due to an increased inwardly rectifying K conductance. The outward current produced by nociceptin was similar to, and occluded by, high concentrations of baclofen, demonstrating a ctions on the same population of K channels. Naloxone (1 mu M) failed to inhibit outward currents produced by nociceptin. These results are consistent with the reported high density of ORL(1) receptor mRNA in d orsal raphe nucleus and with inhibitory actions of nociceptin in cells expressing ORL(1).