Morphine- and CaMKII-dependent enhancement of GIRK channel signaling in hippocampal neurons.
Morphine- and CaMKII-dependent enhancement of GIRK channel signaling in hippocampal neurons.
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DOI：
10.1523/jneurosci.2966-10.2010
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发表时间：
2010-10-06
期刊：
影响因子：
--
通讯作者：
Slesinger PA
中科院分区：
文献类型：
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作者：
Nassirpour R;Bahima L;Lalive AL;Lüscher C;Luján R;Slesinger PA
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 immuno-electron microscopy revealed an increase in GIRK2 protein and targeting to dendritic spines. In vivo administration 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 while 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.
