Morphine- and CaMKII-Dependent Enhancement of GIRK Channel Signaling in Hippocampal Neurons

Autor: Christian Lüscher, Paul A. Slesinger, Rafael Luján, Arnaud L. Lalive, Laia Bahima, Rounak Nassirpour
Rok vydání: 2010
Předmět:
Calcium Signaling/drug effects/physiology
Dendritic spine
medicine.drug_class
Immunoelectron microscopy
Hippocampus/drug effects/enzymology/metabolism
Pharmacology
Pertussis toxin
Hippocampus
Article
Morphine/pharmacology
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Opioid receptor
Ca2+/calmodulin-dependent protein kinase
medicine
Animals
Calcium Signaling
G Protein-Coupled Inwardly-Rectifying Potassium Channels/physiology
G protein-coupled inwardly-rectifying potassium channel
Cells
Cultured
Signal Transduction/drug effects/physiology
030304 developmental biology
Neurons
0303 health sciences
Morphine
General Neuroscience
Morphine Dependence/metabolism/physiopathology
Analgesics
Opioid/pharmacology
Up-Regulation
ddc:616.8
Rats
3. Good health
Analgesics
Opioid
DAMGO
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Animals
Newborn
chemistry
Opioid
Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors/physiology
Up-Regulation/drug effects/physiology
Neurons/drug effects/enzymology/metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Morphine Dependence
030217 neurology & neurosurgery
Signal Transduction
medicine.drug
Zdroj: Journal of Neuroscience, Vol. 30, No 40 (2010) pp. 13419-30
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.2966-10.2010
Popis: G-protein-gated inwardly rectifying potassium (GIRK) channels, which help control neuronal excitability, are important for the response to drugs of abuse. Here, we describe a novel pathway for morphine-dependent enhancement of GIRK channel signaling in hippocampal neurons. Morphine treatment for ∼20 h increased the colocalization of GIRK2 with PSD95, a dendritic spine marker. Western blot analysis and quantitative immunoelectron microscopy revealed an increase in GIRK2 protein and targeting to dendritic spines.In vivoadministration of morphine also produced an upregulation of GIRK2 protein in the hippocampus. The mechanism engaged by morphine required elevated intracellular Ca2+and was insensitive to pertussis toxin, implicating opioid receptors that may couple to Gq G-proteins. Met-enkephalin, but not the μ-selective (DAMGO) and δ-selective (DPDPE) opioid receptor agonists, mimicked the effect of morphine, suggesting involvement of a heterodimeric opioid receptor complex. Peptide (KN-93) inhibition of CaMKII prevented the morphine-dependent change in GIRK localization, whereas expression of a constitutively activated form of CaMKII mimicked the effects of morphine. Coincident with an increase in GIRK2 surface expression, functional analyses revealed that morphine treatment increased the size of serotonin-activated GIRK currents and Ba2+-sensitive basal K+currents in neurons. These results demonstrate plasticity in neuronal GIRK signaling that may contribute to the abusive effects of morphine.
Databáze: OpenAIRE
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