The Inhibition of TREK2 Channel by an Oxidizing Agent, 5,5'-dithio- bis (2-nitrobenzoic acid), via Interaction with the C-terminus Distal to the 353rd Amino Acid.
10.4196/kjpp.2008.12.4.211
- Author:
Kyoung Sun PARK
1
;
Hyoweon BANG
;
Eun Young SHIN
;
Chan Hyung KIM
;
Yangmi KIM
Author Information
1. Division of Molecular and Life Sciences, Hanyang University, Ansan, Korea.
- Publication Type:Original Article
- Keywords:
TREK2;
Oxidizing agent;
5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB);
dithiothreitol (DTT);
C-terminus;
Two-pore domain K+ channel;
K(2P)
- MeSH:
Animals;
Arachidonic Acid;
Chimera;
COS Cells;
Dithionitrobenzoic Acid;
Dithiothreitol;
Membranes;
Oxidants
- From:The Korean Journal of Physiology and Pharmacology
2008;12(4):211-216
- CountryRepublic of Korea
- Language:English
-
Abstract:
TREK (TWIK-RElated K+ channels) and TRAAK (TWIK-Related Arachidonic acid Activated K+ channels) were expressed in COS-7 cells, and the channel activities were recorded from inside-out membrane patches using holding potential of -40 mV in symmetrical 150 mM K+ solution. Intracellular application of an oxidizing agent, 5,5'-dithio-bis (2-nitrobenzoic acid) (DTNB), markedly decreased the activity of the TREK2, and the activity was partially reversed by the reducing agent, dithiothreitol (DTT). In order to examine the possibility that the target sites for the oxidizing agents might be located in the C-terminus of TREK2, two chimeras were constructed: TREK2 (1-383)/TASK3C and TREK2 (1-353)/TASK3C. The channel activity in the TREK2 (1-383)/TASK3C chimera was still inhibited by DTNB, but not in the TREK2 (1-353)/TASK3C chimera. These results indicate that TREK2 is inhibited by oxidation, and that the target site for oxidation is located between the amino acid residues 353 and 383 in the C-terminus of the TREK2 protein.
