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

Dong Ho Woo, Jin Young Bae, Min Ho Nam, Heeyoung An, Yeon Ha Ju, Joungha Won, Jae Hyouk Choi, Eun Mi Hwang, Kyung Seok Han, Yong Chul Bae, Changjoon Lee

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8 Citations (Scopus)

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.

Original languageEnglish
Article number319
JournalFrontiers in Cellular Neuroscience
Volume12
DOIs
Publication statusPublished - 2018 Sep 27

Keywords

  • Astrocyte
  • Glutamate
  • Hippocampus
  • TREK-1
  • μ-opioid receptor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Woo, D. H., Bae, J. Y., Nam, M. H., An, H., Ju, Y. H., Won, J., Choi, J. H., Hwang, E. M., Han, K. S., Bae, Y. C., & Lee, C. (2018). Activation of Astrocytic μ-opioid Receptor Elicits Fast Glutamate Release Through TREK-1-Containing K2P Channel in Hippocampal Astrocytes. Frontiers in Cellular Neuroscience, 12, [319]. https://doi.org/10.3389/fncel.2018.00319