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 language | English |
|---|---|
| Article number | 145 |
| Journal | Experimental and Molecular Medicine |
| Volume | 50 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2018 Nov 1 |
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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 journal › Article
}
TY - JOUR
T1 - TWIK-1/TASK-3 heterodimeric channels contribute to the neurotensin-mediated excitation of hippocampal dentate gyrus granule cells
AU - Choi, Jae Hyouk
AU - Yarishkin, Oleg
AU - Kim, Eunju
AU - Bae, Yeonju
AU - Kim, Ajung
AU - Kim, Seung Chan
AU - Ryoo, Kanghyun
AU - Cho, Chang Hoon
AU - Hwang, Eun Mi
AU - Park, Jae-Yong
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s12276-018-0172-4
DO - 10.1038/s12276-018-0172-4
M3 - Article
VL - 50
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
SN - 1226-3613
IS - 11
M1 - 145
ER -