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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00319

Activation of astrocytic μ-opioid receptor elicits fast glutamate release through TREK-1-containing K2P channel in hippocampal astrocytes

 Dong Ho Woo1, 2, Jin Young Bae3,  Min-Ho Nam1, 4, Heeyoung An1, 5,  Kyung-Seok Han1, 6, Yong Chul Bae3* and  C Justin Lee1, 5, 6*
  • 1Korea Institute of Science and Technology (KIST), South Korea
  • 2Korea Research Institute of Chemical Technology, South Korea
  • 3Kyungpook National University, South Korea
  • 4Kyung Hee University, South Korea
  • 5Korea University, South Korea
  • 6Korea University of Science and Technology, South Korea

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 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-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: astrocyte, μ-opioid receptor, Glutamate, TREK-1, Hippocampus

Received: 05 May 2018; Accepted: 03 Sep 2018.

Edited by:

Carole Escartin, UMR9199 Laboratoire de maladies neurodégénératives mécanismes, thérapies, imagerie, France

Reviewed by:

Martin Oheim, Centre national de la recherche scientifique (CNRS), France
Schuichi Koizumi, University of Yamanashi, Japan  

Copyright: © 2018 Woo, Bae, Nam, An, Han, Bae and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Yong Chul Bae, Kyungpook National University, Daegu, South Korea, ycbae@knu.ac.kr
Dr. C Justin Lee, Korea Institute of Science and Technology (KIST), Bongdong-eup, South Korea, cjl@kist.re.kr