The lipid-activated two-pore domain K+ channel TREK-1 is resistant to hypoxia: implication for ischaemic neuroprotection.
TREK-1 is a member of the two-pore domain potassium (K(2P)) channel family that is mechano-, heat, pH, voltage and lipid sensitive. It is highly expressed in the central nervous system and probably encodes one of the previously described arachidonic acid-activated K(+) channels. Polyunsaturated fatty acids and lysophospholipids protect the brain against global ischaemia. Since both lipids are openers of TREK-1, it has been suggested that this K(2P) channel is directly involved in neuroprotection. Recently, however, this view has been challenged by a report claiming that TREK-1 and its activation by arachidonic acid is inhibited by hypoxia. In the present study, we demonstrate that the bubbling of saline with gases results in the loss of arachidonic acid from solution. Using experimental conditions which obviate this experimental artefact we demonstrate that TREK-1 is resistant to hypoxia and is strongly activated by arachidonic acid even at low P(O(2)) (< 4 Torr). Furthermore, hypoxia fails to affect basal as well as 2,4,6-trinitrophenol- and acid-stimulated TREK-1 currents. These data are supportive for a possible role of TREK-1 in ischaemic neuroprotection and in cell signalling via arachidonic acid.
Buckler
K J
KJ
University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. keith.buckler@physiol.ox.ac.uk
Honoré
E
E
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D019194:Ischemic Preconditioning; D008055:Lipids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018408:Patch-Clamp Techniques; D010851:Picrates / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012996:Solutions; D014162:Transfection
D008055:Lipids; D010851:Picrates; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D012996:Solutions; C103742:potassium channel protein TREK-1; D016718:Arachidonic Acid; C005858:picric acid