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

• Published in: Experimental & molecular medicine Vol. 50; no. 11; pp. 1 - 13
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.11.2018; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13/51; 14/1; 14/35; 38/77; 38/89; 631/378/2586; 631/378/340; 64/60; 82; 9/74; Animals; Biomedical and Life Sciences; Biomedicine; Chlorocebus aethiops; COS Cells; Dendrites; Dentate gyrus; Dentate Gyrus - cytology; Dentate Gyrus - metabolism; Dentate Gyrus - physiology; Depolarization; Excitability; Excitatory Postsynaptic Potentials; Gene silencing; Granule cells; Hippocampus; Localization; Male; Medical Biochemistry; Mice; Mice, Inbred C57BL; Molecular Medicine; Neurons - metabolism; Neurons - physiology; Neurotensin; Neurotensin - metabolism; Potassium channels; Potassium Channels - metabolism; Potassium Channels, Tandem Pore Domain - metabolism; Protein Multimerization; Rodents; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-018-0172-4

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. Nerve cell communication: Controlling excitation Inhibition of potassium channels by the hormone neurotensin (NT) increases the excitability of the dentate gyrus granule cells (DGGCs) of the hippocampus in the mouse brain. A study led by Jae-Yong Park at Korea University and Eun Mi Hwang at Korea Institute of Science and Technology, Seoul, found that the potassium channels TWIK-1 and TASK-3 associate with each other on the membrane of DGGCs. They showed that NT-mediated activation of NT receptor 1 regulates the electrical properties of DGGCs by inhibiting the TWIK-1/TASK-3 complex. This leads to a decrease in the number of potassium ions pumped out of DGGCs and increases in the DGGCs’ ability to transmit information. Further studies on the mechanisms regulating these channels will contribute to our understanding of how they influence information processing in the hippocampus.