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The role of ERK-1/2 in the N/OFQ-induced inhibition of delayed rectifier potassium currents.


Authors: Wei Wang, Qingbo Cui, Yurong Li, Baoxin Li, Xu Yang, Lanwei Cui, Hongbo Jin, Lihui Qu

Journal, date & volume: Biochem. Biophys. Res. Commun., 2010 Apr 16 , 394, 1058-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20331962

Channelpedia reference in: Kv12.1

Abstract
Nociceptin/orphanin FQ (N/OFQ) is an endogenous opioid-like heptadecapeptide involved in many neurocognitive functions, including learning and memory. Our previous report showed that N/OFQ inhibits the delayed rectifier potassium current (I(K)), and this effect is associated with protein kinase C (PKC) activation. Therefore, we wanted to determine if extracellular signal-regulated kinase-1/2 (ERK-1/2) signaling is regulated by N/OFQ and associated with the effect of N/OFQ on the I(K). In the current study, we tested if N/OFQ and two PKC activators [phorbol 12,13-dibutyrate (PDBu) and ingenol 3,20-dibenzoate (IDB)] affected the phosphorylation level of ERK-1/2 and its nuclear substrate, ETS-like transcription factor-1 (Elk-1), using western blots. In addition, we tested if ERK-1/2 affected the N/OFQ-induced inhibition of the I(K) by using whole-cell patch-clamp recordings in acutely dissociated rat parietal cortical neurons. We found that N/OFQ, PDBu, and IDB increased the amount of phosphorylated ERK-1/2 and Elk-1; U0126, a specific inhibitor for ERK-1/2, attenuated the inhibitory effect of N/OFQ on the I(K). These data suggest that the ERK-1/2 pathway, at least in part, mediates the inhibitory effect of N/OFQ on the I(K) in acutely dissociated rat cerebral parietal cortical neurons.