TWIK-1 contributes to the intrinsic excitability of dentate granule cells in mouse hippocampus
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  • 作者:Oleg Yarishkin (1)
    Da Yong Lee (1) (2)
    Eunju Kim (1)
    Chang-Hoon Cho (3)
    Jae Hyouk Choi (1) (4)
    C Justin Lee (1) (4)
    Eun Mi Hwang (1) (4)
    Jae-Yong Park (1) (3)

    1. Korea Institute of Science and Technology (KIST)
    ; Center for Functional Connectomics ; Seoul ; 136-791 ; Republic of Korea
    2. Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    ; Stem Cell Research Center ; Daejeon ; 305-806 ; Republic of Korea
    3. School of Biosystem and Biomedical Science
    ; College of Health Science ; Korea University ; Seoul ; 136-703 ; Republic of Korea
    4. Neuroscience Program
    ; University of Science and Technology (UST) ; Daejeon ; 305-350 ; Republic of Korea
  • 关键词:K2P channel ; TWIK ; 1 ; Intrinsic excitability ; Dentate gyrus granule cell
  • 刊名:Molecular Brain
  • 出版年:2014
  • 出版时间:December 2014
  • 年:2014
  • 卷:7
  • 期:1
  • 全文大小:7,856 KB
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  • 刊物主题:Neurosciences; Neurology;
  • 出版者:BioMed Central
  • ISSN:1756-6606
文摘
Background Two-pore domain K+ (K2P) channels have been shown to modulate neuronal excitability. However, physiological function of TWIK-1, the first identified member of the mammalian K2P channel family, in neuronal cells is largely unknown. Results We found that TWIK-1 proteins were expressed and localized mainly in the soma and proximal dendrites of dentate gyrus granule cells (DGGCs) rather than in distal dendrites or mossy fibers. Gene silencing demonstrates that the outwardly rectifying K+ current density was reduced in TWIK-1-deficient granule cells. TWIK-1 deficiency caused a depolarizing shift in the resting membrane potential (RMP) of DGGCs and enhanced their firing rate in response to depolarizing current injections. Through perforant path stimulation, TWIK-1-deficient granule cells showed altered signal input-output properties with larger EPSP amplitude values and increased spiking compared to control DGGCs. In addition, supra-maximal perforant path stimulation evoked a graded burst discharge in 44% of TWIK-1-deficient cells, which implies impairment of EPSP-spike coupling. Conclusions These results showed that TWIK-1 is functionally expressed in DGGCs and contributes to the intrinsic excitability of these cells. The TWIK-1 channel is involved in establishing the RMP of DGGCs; it attenuates sub-threshold depolarization of the cells during neuronal activity, and contributes to EPSP-spike coupling in perforant path-to-granule cell synaptic transmission.

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