title: Nociceptin/orphanin FQ-induced inhibition of delayed rectifier potassium currents by calcium/calmodulin-dependent protein kinase type II.
abstract: The neuropeptide nociceptin/orphanin FQ (N/OFQ) has been shown to inhibit delayed rectifier potassium current (IK) in acutely dissociated rat parietal cortical neurons. However, the detailed mechanism of N/OFQ-induced inhibition on IK is not clear. This study is the first to explore an involvement of calcium/calmodulin (CaM)-dependent protein kinase type II (CaMKII) in mediating N/OFQ-induced responses. Utilizing pharmacological inhibitors of CaM and CaMKII, we have investigated the contribution of CaMKII in N/OFQ-induced effects using the whole-cell patch-clamp technique. In whole-cell voltage clamp, W-7 (100 μM), an antagonist of CaM, as well as KN-62, an inhibitor of CaMKII activity, attenuated the inhibitory effects of N/OFQ on IK. Activation and inactivation analysis indicated that the kinetics of IK were altered by N/OFQ, with decreased activation and promoted inactivation of IK. W-7 and KN-62 (10 μM) partly abolished the activation and inactivation curves shift of IK induced by N/OFQ. These findings show that CaMKII plays a critical role in N/OFQ-induced inhibition of IK in acutely dissociated rat parietal cortical neurons.
authors.affiliation: aDepartment of Physiology, College of Basic Medical Sciences, Harbin Medical University-Daqing, Daqing bDepartment of Rheumatology and Immunology, First Affiliated Hospital cDepartment of Neurology, Second Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Yue
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.forename: Ruxia
authors.initials: R
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
authors.forename: Qianlong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Lihui
authors.initials: L
authors.lastname: Qu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018847:Opioid Peptides / Q000378:metabolism*; D010296:Parietal Lobe / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D000097629:Nociceptin
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002147:Calmodulin; D004791:Enzyme Inhibitors; D018847:Opioid Peptides; D015221:Potassium Channels; D013449:Sulfonamides; D000097629:Nociceptin; C063302:KN 62; C017967:W 7