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, C. Justin Lee, Jae Yong Park

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

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
Article number3227
JournalNature communications
Volume5
DOIs
Publication statusPublished - 2014 Feb 5

Bibliographical note

Funding Information:
This work was supported by the MRC (2005-0049415) and the World Class Institute (WCI 2009-003) programs of the National Research Foundation (NRF) funded by the Korean Ministry of Science, Education and Technology (MEST), and also supported by National Agenda Project (NAP) of the Korea Research Council of Fundamental Science and Technology (NAP-09-04). We thank George Augustine and Eunmi Hur for careful editing of the manuscript.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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