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Research ArticleArticle

Two-Pore-Domain K+ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Marco Gruss, Trevor J. Bushell, Damian P. Bright, William R. Lieb, Alistair Mathie and Nicholas P. Franks
Molecular Pharmacology February 2004, 65 (2) 443-452; DOI: https://doi.org/10.1124/mol.65.2.443
Marco Gruss
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Trevor J. Bushell
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Damian P. Bright
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William R. Lieb
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Alistair Mathie
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Nicholas P. Franks
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Abstract

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 for these gaseous anesthetics. TREK-1 is markedly activated by clinically relevant concentrations of nitrous oxide, xenon, and cyclopropane. In contrast, TASK-3, a member of this family that is very sensitive to volatile anesthetics, such as halothane, is insensitive to the anesthetic gases. We demonstrate that the C-terminal cytoplasmic domain is not an absolute requirement for the actions of the gases, although it clearly plays an important modulatory role. Finally, we show that Glu306, an amino acid that has previously been found to be important in the modulation of TREK-1 by arachidonic acid, membrane stretch and internal pH, is critical for the activating effects of the anesthetic gases.

  • Received September 15, 2003.
  • Accepted October 30, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 65 (2)
Molecular Pharmacology
Vol. 65, Issue 2
1 Feb 2004
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Research ArticleArticle

Two-Pore-Domain K+ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Marco Gruss, Trevor J. Bushell, Damian P. Bright, William R. Lieb, Alistair Mathie and Nicholas P. Franks
Molecular Pharmacology February 1, 2004, 65 (2) 443-452; DOI: https://doi.org/10.1124/mol.65.2.443

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Research ArticleArticle

Two-Pore-Domain K+ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Marco Gruss, Trevor J. Bushell, Damian P. Bright, William R. Lieb, Alistair Mathie and Nicholas P. Franks
Molecular Pharmacology February 1, 2004, 65 (2) 443-452; DOI: https://doi.org/10.1124/mol.65.2.443
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