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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Citations
Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers.
Thomas M. Suchyna,Sonya E. Tape,Roger E. Koeppe,Olaf S. Andersen,Frederick Sachs,Philip A. Gottlieb +5 more
TL;DR: The results suggest that modulation of membrane proteins by amphipathic peptides—mechanopharmacology—involves not only the protein itself but also the surrounding lipids, and the surprising efficacy of the d form of GsMTx4 has important therapeutic implications, because d peptides are not hydrolysed by endogenous proteases and may be administered orally.
296
Pharmacology of neuronal background potassium channels.
TL;DR: Activation of some of these channels by volatile anaesthetics and by other neuroprotective agents, such as riluzole and unsaturated fatty acids, illustrates how the neuronal background K(+) conductances are attractive targets for the development of new drugs.
280
A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons.
Julie A. Millar,Lynne Barratt,Andrew P. Southan,Karen M. Page,Robert E.W. Fyffe,Brian D. Robertson,Alistair Mathie +6 more
TL;DR: This description of a functional two-pore domain potassium channel in the mammalian central nervous system indicates its physiological importance in controlling cell excitability and how agents that modify its activity, such as agonists at G protein-coupled receptors and hydrogen ions, can profoundly alter both the neuron's resting potential and its excitability.
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•Journal Article
The neuroprotective agent riluzole activates the two P domain K(+) channels TREK-1 and TRAAK.
TL;DR: It is reported that riluzole is an activator of TREK-1 and TRAAK, two important members of a new structural family of mammalian background K(+) channels with four transmembrane domains and two pore regions.
262
Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels
Diana M. Bautista,Yaron M. Sigal,Aaron D. Milstein,Jennifer L. Garrison,Jennifer L. Garrison,Julie A. Zorn,Pamela R. Tsuruda,Pamela R. Tsuruda,Roger A. Nicoll,David Julius +9 more
TL;DR: It is found that hydroxy-α-sanshool excites neurons through a unique mechanism involving inhibition of pH- and anesthetic-sensitive two-pore potassium channels (KCNK3, KCNK9 and KCNK18), providing a framework for understanding the unique and complex psychophysical sensations associated with the Szechuan pepper experience.
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Molecular and cellular mechanisms of general anaesthesia
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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.