title: 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 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.
authors.affiliation: Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. sano.yorikata@yamanouchi.co.jp
authors.forename: Yorikata
authors.initials: Y
authors.lastname: Sano
authors.forename: Kohei
authors.initials: K
authors.lastname: Inamura
authors.forename: Akira
authors.initials: A
authors.lastname: Miyake
authors.forename: Shinobu
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Chika
authors.initials: C
authors.lastname: Kitada
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yokoi
authors.forename: Katsura
authors.initials: K
authors.lastname: Nozawa
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Okada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsushime
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Furuichi
mesh_terms: D000595:Amino Acid Sequence; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004594:Electrophysiology; D004983:Ethanolamines / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008012:Lidocaine / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010802:Phylogeny; D015221:Potassium Channels / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D011405:Propafenone / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D018712:Analgesics, Non-Narcotic; D000889:Anti-Arrhythmia Agents; D004983:Ethanolamines; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; C476574:KCNK18 protein, human; D015221:Potassium Channels; D001464:Barium; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D011405:Propafenone; D008012:Lidocaine; C009546:triethanolamine; D011803:Quinine; D011802:Quinidine; D005905:Glyburide