Document Detail

Nociceptin augments K(+) currents in hippocampal CA1 neurons by both ORL-1 and opiate receptor mechanisms.
MedLine Citation:
PMID:  10515967     Owner:  NLM     Status:  MEDLINE    
We previously reported (see also the accompanying paper) that dynorphin A significantly enhanced the voltage-dependent K(+) M-current (I(M)) in CA3 and CA1 hippocampal pyramidal neurons (HPNs). Because the opioid-receptor-like-1 (ORL-1) receptor shares a high sequence homology with opioid receptors and is expressed in rat hippocampus, we examined the effects of orphanin FQ or nociceptin, the endogenous ligand for the ORL-1 receptor, using the rat hippocampal slice preparation and intracellular voltage-clamp recording. Current-voltage (I-V) relationships from CA1 HPNs revealed that nociceptin superfusion induced an outward current reversing near the equilibrium potential for K(+) ions. Ba(2+) (2 mM) blocked this effect. The nociceptin-induced current was largest at depolarized membrane potentials, where I(M) is largely activated. Nociceptin concentrations of 0.5-1 microM (but not 0.1 microM) significantly increased I(M) relaxation amplitudes with recovery on washout. Interestingly, both the general opiate antagonist naloxone and the kappa receptor antagonist nor-binaltorphimine (nBNI) inhibited the nociceptin-induced I(M) increases and outward currents in the depolarized range but not the inward current induced at hyperpolarized potentials. The putative ORL-1 receptor antagonist, [Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) (hereafter ORLAn), blocked most of the nociceptin current near rest but not the I(M) increase. However, ORLAn alone had direct effects similar to those of nociceptin, indicating that ORLAn might be a partial agonist. Our results suggest that nociceptin postsynaptically modulates the excitability of HPNs through ORL-1 and kappa-like opiate receptors linked to different K(+) channels.
S G Madamba; P Schweitzer; G R Siggins
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurophysiology     Volume:  82     ISSN:  0022-3077     ISO Abbreviation:  J. Neurophysiol.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-05     Completed Date:  1999-11-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375404     Medline TA:  J Neurophysiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1776-85     Citation Subset:  IM    
The Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA.
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MeSH Terms
Barium / pharmacology
Electrophysiology / methods
Hippocampus / physiology*
Membrane Potentials / drug effects
Naloxone / pharmacology
Neurons / drug effects,  physiology*
Opioid Peptides / pharmacology*
Potassium / physiology*
Potassium Channels / drug effects,  physiology*
Rats, Sprague-Dawley
Receptors, Opioid / agonists,  drug effects,  physiology*
Tetrodotoxin / pharmacology
Grant Support
Reg. No./Substance:
0/Opioid Peptides; 0/Potassium Channels; 0/Receptors, Opioid; 0/nociceptin; 0/nociceptin receptor; 4368-28-9/Tetrodotoxin; 465-65-6/Naloxone; 7440-09-7/Potassium; 7440-39-3/Barium

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