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Front Cell Neurosci. 2018 Sep 27;12:319. doi: 10.3389/fncel.2018.00319. eCollection 2018.

Activation of Astrocytic μ-opioid Receptor Elicits Fast Glutamate Release Through TREK-1-Containing K2P Channel in Hippocampal Astrocytes.

Woo DH1,2, Bae JY3, Nam MH1,4, An H1,5, Ju YH1,6, Won J1,7, Choi JH1,6, Hwang EM1,6, Han KS1,6, Bae YC3, Lee CJ1,5,6.

Author information

1
Center for Neural Science and Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, South Korea.
2
Animal Model Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon, South Korea.
3
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, South Korea.
4
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea.
5
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, South Korea.
6
Division of Bio-Medical Science & Technology, Korea Institute of Science and Technology (KIST) School, Korea University of Science and Technology, Seoul, South Korea.
7
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.

Abstract

Recently, μ-opioid receptor (MOR), one of the well-known Gi-protein coupled receptors (Gi-GPCR), was reported to be highly expressed in the hippocampal astrocytes. However, the role of astrocytic MOR has not been investigated. Here we report that activation of astrocytic MOR by [D-Ala2,N-MePhe4,Gly-ol]-enkephalin (DAMGO), a selective MOR agonist, causes a fast glutamate release using sniffer patch technique. We also found that the DAMGO-induced glutamate release was not observed in the astrocytes from MOR-deficient mice and MOR-short hairpin RNA (shRNA)-expressed astrocytes. In addition, the glutamate release was significantly reduced by gene silencing of the TREK-1-containing two-pore potassium (K2P) channel, which mediates passive conductance in astrocytes. Our findings were consistent with the previous study demonstrating that activation of Gi-GPCR such as cannabinoid receptor CB1 and adenosine receptor A1 causes a glutamate release through TREK-1-containing K2P channel from hippocampal astrocytes. We also demonstrated that MOR and TREK-1 are significantly co-localized in the hippocampal astrocytes. Furthermore, we found that both MOR and TREK-1-containing K2P channels are localized in the same subcellular compartments, soma and processes, of astrocytes. Our study raises a novel possibility that astrocytic MOR may participate in several physiological and pathological actions of opioids, including analgesia and addiction, through astrocytically released glutamate and its signaling pathway.

KEYWORDS:

TREK-1; astrocyte; glutamate; hippocampus; μ-opioid receptor

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