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

Eun Mi Hwang, Eunju Kim, Oleg Yarishkin, Dong Ho Woo, Kyung Seok Han, Nammi Park, Yeonju Bae, Junsung Woo, Donggyu Kim, Myeongki Park, Changjoon Lee, Jae-Yong Park

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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.

Original languageEnglish
Pages (from-to)3227
Number of pages1
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 2014
Externally publishedYes

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disulfides
Astrocytes
Disulfides
membranes
glutamates
Cannabinoids
Gene Silencing
Cell membranes
genes
Membrane Potentials
Glutamic Acid
Carrier Proteins
Genes
Cell Membrane
potassium channel protein TREK-1
proteins
Membranes
porosity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. / Mi Hwang, Eun; Kim, Eunju; Yarishkin, Oleg; Ho Woo, Dong; Han, Kyung Seok; Park, Nammi; Bae, Yeonju; Woo, Junsung; Kim, Donggyu; Park, Myeongki; Lee, Changjoon; Park, Jae-Yong.

In: Nature Communications, Vol. 5, 2014, p. 3227.

Research output: Contribution to journalArticle

Mi Hwang, E, Kim, E, Yarishkin, O, Ho Woo, D, Han, KS, Park, N, Bae, Y, Woo, J, Kim, D, Park, M, Lee, C & Park, J-Y 2014, 'A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes', Nature Communications, vol. 5, pp. 3227. https://doi.org/10.1038/ncomms4227
Mi Hwang, Eun ; Kim, Eunju ; Yarishkin, Oleg ; Ho Woo, Dong ; Han, Kyung Seok ; Park, Nammi ; Bae, Yeonju ; Woo, Junsung ; Kim, Donggyu ; Park, Myeongki ; Lee, Changjoon ; Park, Jae-Yong. / A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. In: Nature Communications. 2014 ; Vol. 5. pp. 3227.
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