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A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

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  • Eun Mi Hwang

    (Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
    WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST)
    Neuroscience Program, University of Science and Technology (UST))

  • Eunju Kim

    (Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
    WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST))

  • Oleg Yarishkin

    (WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST))

  • Dong Ho Woo

    (WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST)
    Neuroscience Program, University of Science and Technology (UST))

  • Kyung-Seok Han

    (WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST)
    Neuroscience Program, University of Science and Technology (UST))

  • Nammi Park

    (Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine)

  • Yeonju Bae

    (WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST))

  • Junsung Woo

    (WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST)
    Neuroscience Program, University of Science and Technology (UST))

  • Donggyu Kim

    (Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine)

  • Myeongki Park

    (WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST)
    Neuroscience Program, University of Science and Technology (UST))

  • C. Justin Lee

    (WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST)
    Neuroscience Program, University of Science and Technology (UST)
    KU-KIST Graduate School of Converging Science of Technology)

  • Jae-Yong Park

    (Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine
    WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST))

Abstract

TWIK-1 is a member of the two-pore domain K+ (K2P) channel family that plays an essential part in the regulation of resting membrane potential and cellular excitability. The physiological role of TWIK-1 has remained enigmatic because functional expression of TWIK-1 channels is elusive. Here we report that native TWIK-1 forms a functional channel at the plasma membrane of astrocytes. A search for TWIK-1-binding proteins led to the identification of TREK-1, another member of the K2P family. The TWIK-1/TREK-1 heterodimeric channel is formed via a disulphide bridge between residue C69 in TWIK-1 and C93 in TREK-1. Gene silencing demonstrates that surface expression of TWIK-1 and TREK-1 are interdependent. TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels.

Suggested Citation

  • Eun Mi Hwang & Eunju Kim & Oleg Yarishkin & Dong Ho Woo & Kyung-Seok Han & Nammi Park & Yeonju Bae & Junsung Woo & Donggyu Kim & Myeongki Park & C. Justin Lee & Jae-Yong Park, 2014. "A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes," Nature Communications, Nature, vol. 5(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4227
    DOI: 10.1038/ncomms4227
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    Cited by:

    1. Yoshiaki Suzuki & Kanako Tsutsumi & Tatsuya Miyamoto & Hisao Yamamura & Yuji Imaizumi, 2017. "Heterodimerization of two pore domain K+ channel TASK1 and TALK2 in living heterologous expression systems," PLOS ONE, Public Library of Science, vol. 12(10), pages 1-17, October.

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