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

• Published in: The Journal of biological chemistry Vol. 278; no. 30; pp. 27406 - 27412
• Main Authors: Sano, Yorikata, Inamura, Kohei, Miyake, Akira, Mochizuki, Shinobu, Kitada, Chika, Yokoi, Hiromichi, Nozawa, Katsura, Okada, Hidetsugu, Matsushime, Hitoshi, Furuichi, Kiyoshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.07.2003; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Analgesics, Non-Narcotic - pharmacology; Animals; Anti-Arrhythmia Agents - pharmacology; Arachidonic Acid - pharmacology; Barium - pharmacology; Cell Line; Cloning, Molecular; Docosahexaenoic Acids - pharmacology; Electrophysiology; Ethanolamines - pharmacology; Fatty Acids - metabolism; Fatty Acids, Nonesterified - metabolism; Glyburide - pharmacology; Humans; Hydrogen-Ion Concentration; Lidocaine - pharmacology; Mice; Models, Biological; Molecular Sequence Data; Patch-Clamp Techniques; Phylogeny; Potassium Channels - biosynthesis; Potassium Channels - chemistry; Potassium Channels - physiology; Propafenone - pharmacology; Protein Structure, Tertiary; Quinidine - pharmacology; Quinine - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Spinal Cord - metabolism; Tissue Distribution; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M206810200

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 two-pore 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 Ba2+, 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.