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

Hwang, Eun Mi; Kim, Eunju; Yarishkin, Oleg; Woo, Dong Ho; Han, Kyung-Seok; Park, Nammi; Bae, Yeonju; Woo, Junsung et al. · Nat Commun · 2014

basic_science · Level V

Where this comes from

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.

Medical subject headings