The effects of hypoxia on the modulation of human TREK-1 potassium channels.
Two-pore-domain potassium channels are a family of ion channels that are widely believed to play an important role in maintaining and regulating neuronal excitability. It has been shown that they can be modulated by an extraordinarily diverse range of endogenous and exogenous factors. One particular member of the family, TREK-1 (also known as KCNK2), is activated by increasing temperature, membrane stretch and internal acidosis, but is also sensitive to the presence of certain polyunsaturated fatty acids (such as arachidonic acid), neuroprotectants (such as riluzole) and volatile and gaseous general anaesthetics (such as halothane and nitrous oxide). It has recently been reported that TREK-1 channels are also affected by oxygen concentrations, and that at the levels of hypoxia that occur in the normal human brain, the channels greatly change their properties and, for example, lose their ability to be modulated by arachidonic acid and internal acidosis. These reports seriously challenge the idea that TREK-1 is a target for general anaesthetics and neuroprotectants. However, in this report we show that TREK-1 is not oxygen sensitive, and its ability to be activated by anaesthetics, arachidonic acid and internal acidosis remains unaltered under conditions of hypoxia. We further show that the protocol used by previous workers to prepare hypoxic solutions of arachidonic acid results in the removal of the compound from solution.
Caley
Alex J
AJ
Biophysics Section, The Blackett Laboratory, Imperial College, London SW7 2AZ, UK.
Gruss
Marco
M
Franks
Nicholas P
NP
D000138:Acidosis / Q000503:physiopathology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D002460:Cell Line; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*
D018685:Anesthetics, Inhalation; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D016718:Arachidonic Acid; D010100:Oxygen; D006221:Halothane