Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane.

@article{Gruss2004TwoporedomainKC,
  title={Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane.},
  author={Marco Gruss and Trevor J Bushell and Damian P. Bright and William Robert Lieb and Alistair Mathie and Nicholas P. Franks},
  journal={Molecular pharmacology},
  year={2004},
  volume={65 2},
  pages={
          443-52
        }
}
Nitrous oxide, xenon, and cyclopropane are anesthetic gases that have a distinct pharmacological profile. Whereas the molecular basis for their anesthetic actions remains unclear, they behave very differently to most other general anesthetics in that they have little or no effect on GABAA receptors, yet strongly inhibit the N-methyl-d-aspartate subtype of glutamate receptors. Here we show that certain members of the two-pore-domain K+ channel superfamily may represent an important new target… Expand
Therapeutic potential of neuronal two-pore domain potassium-channel modulators.
TLDR
The diversity and physiological importance of K2P channels suggest that the development of selective compounds to target these proteins has therapeutic potential for CNS disorders such as stroke, depression and epilepsy. Expand
Halogenated Ether, Alcohol, and Alkane Anesthetics Activate TASK-3 Tandem Pore Potassium Channels Likely through a Common Mechanism
TLDR
The TWIK-related acid-sensitive potassium channel 3 (TASK-3; KCNK9) tandem pore potassium channel function is activated by halogenated anesthetics through binding at a putative anesthetic-binding cavity through mutagenesis and the residue Val-136 and adjacent residues may mediate anesthetic binding and stabilize an open state regulated by pore residue Leu-122. Expand
Noble Gas Xenon Is a Novel Adenosine Triphosphate-sensitive Potassium Channel Opener
TLDR
Through this action and by its ability to readily partition across the blood–brain barrier, xenon has considerable potential in clinical settings of neuronal injury, including stroke. Expand
Protein crystallography under xenon and nitrous oxide pressure: comparison with in vivo pharmacology studies and implications for the mechanism of inhaled anesthetic action.
TLDR
It is proposed that alterations of cytosolic globular protein functions by general anesthetics would be responsible for the early stages of anesthesia such as amnesia and hypnosis and that additional alterations of ion-channel membrane receptor functions are required for deeper effects that progress to "surgical" anesthesia. Expand
N-Methyl-d-Aspartate Receptor Channel Blocker–Like Discriminative Stimulus Effects of Nitrous Oxide Gas
TLDR
The results support the hypothesis that the discriminative stimulus effects of N2O are at least partially mediated by NMDA antagonist effects similar to those produced by channel blockers, however, as none of the drugs tested fully mimicked the stimulus results of N 2O, other mechanisms may also be involved. Expand
Nitrous oxide (N(2)O) requires the N-methyl-D-aspartate receptor for its action in Caenorhabditis elegans.
  • P. Nagele, L. Metz, C. Crowder
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2004
TLDR
The behavioral effects of N(2)O require the NMDA receptor NMR-1, consistent with the hypothesis formed from vertebrate electrophysiological data that a major target of N2O is theNMDA receptor. Expand
Studies on the mechanism of general anesthesia
TLDR
It is shown that inhaled anesthetics (chloroform and isoflurane) activate TREK-1 channels through disruption of ordered lipid domains (rafts) and suggests a two-step model of anesthetic TREk-1 activation. Expand
Competitive Inhibition at the Glycine Site of the N-Methyl-d-Aspartate Receptor Mediates Xenon Neuroprotection against Hypoxia–Ischemia
TLDR
It is shown that xenon neuroprotection against hypoxia– ischemia can be reversed by increasing the glycine concentration, consistent with competitive inhibition by xenon at the NMDA receptor glycine site, playing a significant role in xenon Neuroprotection. Expand
Pressure‐response analysis of anesthetic gases xenon and nitrous oxide on urate oxidase: a crystallographic study
  • G. Marassio, T. Prangé, +5 authors N. Colloc'h
  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2011
TLDR
It is shown that Xe and N2O bind to, compete for, and expand the volume of a hydrophobic cavity located just behind the active site of urate oxidase and further inhibit urate oxidation activity, highlighting the mechanisms by which chemically and metabolically inert gases can alter protein function and produce their pharmacological effects. Expand
Xenon Acts by Inhibition of Non–N-methyl-d-aspartate Receptor–mediated Glutamatergic Neurotransmission in Caenorhabditis elegans
TLDR
Xenon acts in Caenorhabditis elegans to alter locomotion through a mechanism requiring the non-NMDA glutamate receptor encoded by glr-1, unlike for the action of nitrous oxide in C. elegans, the NMDA receptors encoded by nmR-1 is not essential for sensitivity to xenon. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 47 REFERENCES
The TASK-1 Two-Pore Domain K+ Channel Is a Molecular Substrate for Neuronal Effects of Inhalation Anesthetics
TLDR
Evidence is presented implicating the two-pore domain, pH-sensitive TASK-1 channel as a target for specific, clinically important anesthetic effects in mammalian neurons, in rat somatic motoneurons and locus coeruleus cells. Expand
Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels: Comparison with Isoflurane and Ethanol
TLDR
The results suggest that NMDA receptors and nACh receptors composed of &bgr;2 subunits are likely targets for nitrous oxide and xenon, which are distinct from that of isoflurane or ethanol. Expand
Anesthetic-sensitive 2P Domain K+ Channels
TLDR
The expression and properties of these anesthetic-sensitive K channels are reviewed, and their possible functional role in the mechanisms of anesthesia and analgesia is discussed. Expand
Inhalational anesthetics activate two-pore-domain background K+ channels
TLDR
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. Expand
Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) Potassium Channels
TLDR
Both anesthetic activation and transmitter inhibition of these channels require a region at the interface between the final transmembrane domain and the cytoplasmic C terminus that has not been associated previously with receptor signal transduction. Expand
Volatile general anaesthetics activate a novel neuronal K+ current
TLDR
It is reported that amongst a group of apparently identical molluscan neurons having endogenous firing activity, a single cell displays an unusual sensitivity to volatile agents (which, at surgical levels, completely inhibit its activity); it is shown that this sensitivity is due to a novel anaesthetic-activated K+ current, which is found in the sensitive cell but not in the surrounding insensitive cells. Expand
TOK1 Is a Volatile Anesthetic Stimulated K+ Channel
TLDR
To investigate whether cloned ion channels with electrophysiologic properties similar to the S channel also are modulated by volatile anesthetic agents, cloned yeast ion channel TOK1 was expressed in Xenopus oocytes and studied its sensitivity to volatile agents. Expand
Anesthetics and ion channels: molecular models and sites of action.
TLDR
This review summarizes from a molecular perspective recent advances in the understanding of mechanisms of action of general anesthetics on ligand-gated ion channels. Expand
Mechano- or Acid Stimulation, Two Interactive Modes of Activation of the TREK-1 Potassium Channel*
TLDR
It is shown that internal acidification opens TREK-1, a member of the novel structural class of K+ channels with four transmembrane segments and two pore domains in tandem, and lowering pH i shifts the pressure-activation relationship toward positive values and leads to channel opening at atmospheric pressure. Expand
A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons.
  • J. Millar, L. Barratt, +4 authors A. Mathie
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2000
TLDR
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. Expand
...
1
2
3
4
5
...