High impact information on KCNK18

• Here we report a novel two-pore domain K+ channel, TRESK (TWIK-related spinal cord K+ channel) [1].
• 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 [1].
• Pharmacological analysis showed TRESK to be inhibited by previously reported K+ channel inhibitors Ba2+, propafenone, glyburide, lidocaine, quinine, quinidine, and triethanolamine [1].
• Functional analysis demonstrated TRESK to be inhibited by unsaturated free fatty acids such as arachidonic acid and docosahexaenoic acid [1].
• 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 [1].

Anatomical context of KCNK18

• Moreover, we confirmed that TRESK is expressed in the spinal cord [1].
• These results identify TRESK as a target of volatile anesthetics and suggest a role for this background K channel in mediating the effects of inhaled anesthetics in the central nervous system [2].
• We isolated the coding sequence for TRESK from human spinal cord RNA and functionally expressed it in Xenopus oocytes and transfected COS-7 cells [2].

Associations of KCNK18 with chemical compounds

• In particular, we found stereospecific differences in response to isoflurane by the rodent TRESKs but not by human TRESK [3].
• Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic-activated K2P channel yet described [3].
• Various IV anesthetics, including etomidate, thiopental, and propofol, have a minimal effect on TRESK currents [2].

References