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TWIK-1/TASK-3 heterodimeric channels contribute to the neurotensin-mediated excitation of hippocampal dentate gyrus granule cells

  • Choi, Jae Hyouk (Korea Institute of Science and Technology (KIST), Center for Functional Connectomics) ;
  • Yarishkin, Oleg (Korea Institute of Science and Technology (KIST), Center for Functional Connectomics) ;
  • Kim, Eunju (Korea Institute of Science and Technology (KIST), Center for Functional Connectomics) ;
  • Bae, Yeonju (School of Biosystem and Biomedical Science, College of Health Science, Korea University) ;
  • Kim, Ajung (Korea Institute of Science and Technology (KIST), Center for Functional Connectomics) ;
  • Kim, Seung-Chan (Korea Institute of Science and Technology (KIST), Center for Functional Connectomics) ;
  • Ryoo, Kanghyun (School of Biosystem and Biomedical Science, College of Health Science, Korea University) ;
  • Cho, Chang-Hoon (School of Biosystem and Biomedical Science, College of Health Science, Korea University) ;
  • Hwang, Eun Mi (Korea Institute of Science and Technology (KIST), Center for Functional Connectomics) ;
  • Park, Jae-Yong (School of Biosystem and Biomedical Science, College of Health Science, Korea University)
  • Received : 2018.01.04
  • Accepted : 2018.07.23
  • Published : 2018.11.30

Abstract

Two-pore domain $K^+$ (K2P) channels have been shown to modulate neuronal excitability. The physiological role of TWIK-1, the first identified K2P channel, in neuronal cells is largely unknown, and we reported previously that TWIK-1 contributes to the intrinsic excitability of dentate gyrus granule cells (DGGCs) in mice. In the present study, we investigated the coexpression of TWIK-1 and TASK-3, another K2P member, in DGGCs. Immunohistochemical staining data showed that TASK-3 proteins were highly localized in the proximal dendrites and soma of DGGCs, and this localization is similar to the expression pattern of TWIK-1. TWIK-1 was shown to associate with TASK-3 in DGGCs of mouse hippocampus and when both genes were overexpressed in COS-7 cells. shRNA-mediated gene silencing demonstrated that TWIK-1/TASK-3 heterodimeric channels displayed outwardly rectifying currents and contributed to the intrinsic excitability of DGGCs. Neurotensin-neurotensin receptor 1 (NT-NTSR1) signaling triggered the depolarization of DGGCs by inhibiting TWIK-1/TASK-3 heterodimeric channels, causing facilitated excitation of DGGCs. Taken together, our study clearly showed that TWIK-1/TASK-3 heterodimeric channels contribute to the intrinsic excitability of DGGCs and that their activities are regulated by NT-NTSR1 signaling.

Keywords

Acknowledgement

Supported by : National Research Foundation (NRF) of Korea, KIST

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