Journal Article10.1038/8084
Inhalational anesthetics activate two-pore-domain background K+ channels.
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TL;DR: It is shown that TASK and TREK-1, two recently cloned mammalian two-P-domain K+ channels similar to IKAn in biophysical properties, are activated by volatile general anesthetics.
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Abstract: Volatile anesthetics produce safe, reversible unconsciousness, amnesia and analgesia via hyperpolarization of mammalian neurons. In molluscan pacemaker neurons, they activate an inhibitory synaptic K+ current (IKAn), proposed to be important in general anesthesia. Here we show that TASK and TREK-1, two recently cloned mammalian two-P-domain K+ channels similar to IKAn in biophysical properties, are activated by volatile general anesthetics. Chloroform, diethyl ether, halothane and isoflurane activated TREK-1, whereas only halothane and isoflurane activated TASK. Carboxy (C)-terminal regions were critical for anesthetic activation in both channels. Thus both TREK-1 and TASK are possibly important target sites for these agents.
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References
Molecular and cellular mechanisms of general anaesthesia
TL;DR: It is now clear that anaesthetics act directly on proteins rather than on lipids, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia.
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Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
S. John Mihic,S. John Mihic,Qing Ye,Marilee J. Wick,Marilee J. Wick,Vladimir V. Koltchine,Matthew D. Krasowski,Suzanne E. Finn,Maria Paola Mascia,C. Fernando Valenzuela,Kirsten K. Hanson,Eric P. Greenblatt,R. Adron Harris,R. Adron Harris,Neil L. Harrison +14 more
TL;DR: Observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetic action.
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TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure.
Florian Lesage,Eric Guillemare,Michel Fink,Fabrice Duprat,Michel Lazdunski,Georges Romey,Jacques Barhanin +6 more
TL;DR: A weakly inward rectifying K+ channel, TWIK-1, has been isolated in Xenopus oocytes as discussed by the authors, which has four transmembrane domains and a unitary conductance of 34 pS and a kinetic behavior that is dependent on the membrane potential.
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Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel.
Michel Fink,Fabrice Duprat,Florian Lesage,Roberto V. Reyes,Georges Romey,Catherine Heurteaux,Michel Lazdunski +6 more
TL;DR: The results provide the first evidence for the existence of a K+ channel family with four TMS and two pore domains in the nervous system of mammals and show that different members in this structural family can have totally different functional properties.
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A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids
Michel Fink,Florian Lesage,Fabrice Duprat,Catherine Heurteaux,Roberto V. Reyes,Michel Fosset,Michel Lazdunski +6 more
TL;DR: The cloning of TRAAK, a 398 amino acid protein which is a new member of this mammalian class of K+ channels, is reported, which can be stimulated by arachidonic acid and other unsaturated fatty acids but not by saturated fatty acids.