A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes.
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.
1] Department of Physiology, Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea [2] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [3] Neuroscience Program, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea [4].
Eun Mi
EM
Hwang
1] Department of Physiology, Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea [2] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [3].
Eunju
E
Kim
WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
Oleg
O
Yarishkin
1] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [2] Neuroscience Program, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea.
Dong Ho
DH
Woo
1] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [2] Neuroscience Program, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea.
Kyung-Seok
KS
Han
Department of Physiology, Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
Nammi
N
Park
WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
Yeonju
Y
Bae
1] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [2] Neuroscience Program, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea.
Junsung
J
Woo
Department of Physiology, Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
Donggyu
D
Kim
1] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [2] Neuroscience Program, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea.
Myeongki
M
Park
1] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea [2] Neuroscience Program, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea [3] KU-KIST Graduate School of Converging Science of Technology, Seoul 136-701, Republic of Korea.
C Justin
CJ
Lee
1] Department of Physiology, Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea [2] WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
Jae-Yong
JY
Park
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D019281:Dimerization; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1
C109137:KCNK1 protein, human; D024683:Potassium Channels, Tandem Pore Domain; D043884:Receptor, Cannabinoid, CB1; C103742:potassium channel protein TREK-1; D018698:Glutamic Acid; D011188:Potassium