Effects of PKC on inhibition of delayed rectifier potassium currents by N/OFQ

Abstract 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 I K 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 μM) resulted in a dose-dependent depression of I K with partially recovery on washout. Furthermore, we investigated the role of PKC in the inhibition of I K by N/OFQ. Chelerythrine, an inhibitor of PKC, attenuated the inhibition of N/OFQ on I K . On the contrary, PDBu, an activator of PKC, augmented N/OFQ-evoked responses. The present study suggested that N/OFQ inhibited I K and PKC was involved in N/OFQ-evoked response in acutely dissociated rat cerebral parietal cortical neurons.