Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid receptor-like-1 (ORL-1) orphan receptor, which is responsible for inhibition of delayed rectifier potassium current (I-K). But its mechanism of N/OFQ acting on IK is not clear and whether PKC is involved in the modulation of this processing is still unknown. Whole-cell patch-clamp recordings were performed in acutely dissociated rat parietal cortical neurons. Bath application of N/OFQ (10 nM-10 mu M) resulted in a dose-dependent depression of IK with partially recovery on washout. Furthermore, we investigated the role of PKC in the inhibition of IK by N/OFQ. Chelerythrine, an inhibitor of PKC, attenuated the inhibition of N/OFQ on IK. On the contrary, PDBu, an activator of PKC, augmented N/OFQ-evoked responses. The present study suggested that N/OFQ inhibited IK and PKC was involved in N/OFQ-evoked response in acutely dissociated rat cerebral parietal cortical neurons. (c) 2007 Elsevier Inc. All rights reserved.