Increase by the ORL(1) receptor (opioid receptor-like(1)) ligand, nociceptin, of inwardly rectifying K conductance in dorsal raphe nucleus neurones

The actions of the endogenous ORL(1)-receptor (opioid receptor-like(1)) ligand, nociceptin, on the membrane properties of rat dorsal raphe nucleus neurones were examined by use of whole-cell patch clamp recording in brain slices. Nociceptin produced an outward current in all neurones 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 nociceptin-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 actions 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 dorsal raphe nucleus and with inhibitory actions of nociceptin in cells expressing ORL(1).