title: TASK channels contribute to neuroprotective action of inhalational anesthetics.
abstract: Postconditioning with inhalational anesthetics can reduce ischemia-reperfusion brain injury, although the cellular mechanisms for this effect have not been determined. The current study was designed to test if TASK channels contribute to their neuroprotective actions. Whole cell recordings were used to examine effects of volatile anesthetic on TASK currents in cortical neurons and to verify loss of anesthetic-activated TASK currents from TASK-/-mice. A transient middle cerebral artery occlusion (tMCAO) model was used to establish brain ischemia-reperfusion injury. Quantitative RT-PCR analysis revealed that TASK mRNA was reduced by >90% in cortex and hippocampus of TASK-/-mice. The TASK-/-mice showed a much larger region of infarction than C57BL/6 J mice after tMCAO challenge. Isoflurane or sevoflurane administered after the ischemic insult reduced brain infarct percentage and neurological deficit scores in C57BL/6 J mice, these effect were reduced in TASK-/-mice. Whole cell recordings revealed that the isoflurane-activated background potassium current observed in cortical pyramidal neurons from wild type mice was conspicuously reduced in TASK-/-mice. Our studies demonstrate that TASK channels can limit ischemia-reperfusion damage in the cortex, and postconditioning with volatile anesthetics provides neuroprotective actions that depend, in part, on activation of TASK currents in cortical neurons.
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China.
authors.forename: Chengye
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Linyi People's Hospital, Shandong, 276000 China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China.
authors.forename: Shaofang
authors.initials: S
authors.lastname: Shu
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China.
authors.forename: Shanglong
authors.initials: S
authors.lastname: Yao
authors.affiliation: Departments of Anesthesiology, University of Virginia, Charlottesville, 22901 Virginia, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Lynch
authors.affiliation: Departments of Pharmacology and Anesthesiology, University of Virginia, Charlottesville, 22901 Virginia, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bayliss
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D007530:Isoflurane / Q000494:pharmacology*; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D000077149:Sevoflurane; D007530:Isoflurane