A Novel Two-pore Domain K+ Channel, TRESK, Is Localized in the Spinal Cord

Abstract

To find a novel human ion channel gene we have executed an extensive search by using a human genome draft sequencing data base. Here we report a novel twopore domain K ؉ channel, TRESK (TWIK-related spinal cord K ؉ channel). TRESK is coded by 385 amino acids and shows low homology (19%) with previously characterized two-pore domain K ؉ channels. However, the most similar channel is TREK-2 (two-pore domain K ؉ channel), and TRESK also has two pore-forming domains and four transmembrane domains that are evolutionarily conserved in the two-pore domain K ؉ channel family. Moreover, we confirmed that TRESK is expressed in the spinal cord. Electrophysiological analysis demonstrated that TRESK induced outward rectification and functioned as a background K ؉ channel. Pharmacological analysis showed TRESK to be inhibited by previously reported K ؉ channel inhibitors Ba 2؉ , propafenone, glyburide, lidocaine, quinine, quinidine, and triethanolamine. Functional analysis demonstrated TRESK to be inhibited by unsaturated free fatty acids such as arachidonic acid and docosahexaenoic acid. TRESK is also sensitive to extreme changes in extracellular and intracellular pH. These results indicate that TRESK is a novel two-pore domain K ؉ channel that may set the resting membrane potential of cells in the spinal cord.

Functional Expression of TRESK-2, a New Member of the Tandem-pore K+ Channel Family

“…DISCUSSION We have cloned a new member of the K 2p channel family and studied its tissue expression and electrophysiological properties. We named it TRESK-2 because it shares 63% amino acid identity with TRESK-1, which was cloned recently (21). The cloning of TRESK-2 brings the number of mammalian K 2P channels to a total of 16.…”

“…3B). Clearly, these results show that in human, TRESK-2 mRNA is more widely expressed than TRESK-1 mRNA, which was detected only in the spinal cord among the 23 tissues examined (21). Whole-cell Current Recordings-To determine whether TRESK-2 forms a functional K ϩ channel, we first recorded whole-cell currents from COS-7 cells transfected with plasmids containing TRESK-2 and GFP DNA fragments.…”

“…The most recently identified member of the K 2P channel family is TRESK-1 (TWIK-related spinal cord K ϩ channel), named so because its mRNA was expressed solely in the human spinal cord (21). When expressed in L929 cells, TRESK-1 has been reported to form a functional K ϩ channel that has properties of a background (or leak) K ϩ channel.…”

“…Each subunit of a K 2P channel possesses four TM segments and two P domains, and therefore two subunits are thought to assemble to form a functional dimeric K ϩ channel (4,5). K 2P channels can be divided into six subfamilies based on amino acid homology: TWIK-1 and TWIK-2 (6 -9); THIK-1 and THIK-2 (10); TASK-1, TASK-3, and TASK-5 (11-13); TALK-1, TASK-2, and TALK-2 (14 -16); TREK-1, TREK-2, and TRAAK (17)(18)(19)(20); and TRESK-1 (21). Many of these K 2P channel are able to form functional K ϩ channels when expressed in oocytes or mammalian cells.…”

Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1

“…To date, 17 human K2P channel subunits have been identified according to their amino acid sequence identity and regulatory mechanisms. They can be divided into six subfamilies: TWIK, THIK, TASK, TALK, TREK, and TRESK [5,6] .…”