title: Modulation of hTREK-1 by carbon monoxide.
abstract: TREK-1 is a background K channel important in the regulation of neuronal excitability. Here, we demonstrate that recombinant human TREK-1 is activated by low concentrations of carbon monoxide (CO) and nitric oxide (NO), applied via their respective donor molecules. Related channels hTASK-1 and hTASK-3 were unaffected by CO. Effects of both CO and NO were prevented by preincubation of cells with the protein kinase G inhibitor, Rp-8-Br-PET-cGMPS. The effects of CO were independent of NO formation. At higher concentrations, both NO and CO were inhibitory. As both NO and CO are important neuronal gasotransmitters and TREK is crucial in regulating neuronal excitability, our results provide a novel means by which these gases may modulate neuronal activity.
authors.affiliation: Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Dallas
authors.forename: Jason L
authors.initials: JL
authors.lastname: Scragg
authors.forename: Chris
authors.initials: C
authors.lastname: Peers
mesh_terms: D002248:Carbon Monoxide / Q000494:pharmacology*; D002460:Cell Line; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C498655:KCNK9 protein, human; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins; C103742:potassium channel protein TREK-1; C447082:tricarbonyldichlororuthenium (II) dimer; C420132:potassium channel subfamily K member 3; D009569:Nitric Oxide; C002385:linsidomine; D002248:Carbon Monoxide; D008981:Molsidomine; D017869:Cyclic GMP-Dependent Protein Kinases