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

Jae Hyouk Choi, Oleg Yarishkin, Eunju Kim, Yeonju Bae, Ajung Kim, Seung Chan Kim, Kanghyun Ryoo, Chang Hoon Cho, Eun Mi Hwang, Jae-Yong Park

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number145
JournalExperimental and Molecular Medicine
Volume50
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

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Neurotensin
Parahippocampal Gyrus
Dentate Gyrus
Genes
Depolarization
Carisoprodol
Small Interfering RNA
Proteins
COS Cells
Gene Silencing
Dendrites
Hippocampus
Staining and Labeling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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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; Yarishkin, Oleg; Kim, Eunju; Bae, Yeonju; Kim, Ajung; Kim, Seung Chan; Ryoo, Kanghyun; Cho, Chang Hoon; Hwang, Eun Mi; Park, Jae-Yong.

In: Experimental and Molecular Medicine, Vol. 50, No. 11, 145, 01.11.2018.

Research output: Contribution to journalArticle

Choi, Jae Hyouk ; Yarishkin, Oleg ; Kim, Eunju ; Bae, Yeonju ; Kim, Ajung ; Kim, Seung Chan ; Ryoo, Kanghyun ; Cho, Chang Hoon ; Hwang, Eun Mi ; Park, Jae-Yong. / TWIK-1/TASK-3 heterodimeric channels contribute to the neurotensin-mediated excitation of hippocampal dentate gyrus granule cells. In: Experimental and Molecular Medicine. 2018 ; Vol. 50, No. 11.
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AU - Bae, Yeonju

AU - Kim, Ajung

AU - Kim, Seung Chan

AU - Ryoo, Kanghyun

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