Cited by 655Ion channel regulation and functionAnesthesia and Sedative AgentsAnesthesia and Neurotoxicity Research

Inhalational anesthetics activate two-pore-domain background K+ channels

Patel, Amanda J., Honoré, Eric, Lesage, Florian, Fink, Michel, Romey, Georges, Lazdunski, Michel·1999·Nature Neuroscience

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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Crossref · 10.1038/8084

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  • The K2P family includes mammalian homologues activated by anesthetics and others inhibited by anesthetics.

    “Subsequent work led to the discovery of the tandem pore potassium channel (K2P) family, which contains mammalian homologues that are activated by anesthetics [48]) as well as those that are inhibited by anesthetics [49, 50].”

    From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [50]

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Authors
Patel, A. J., Honoré, E., Lesage, F., Fink, M., Romey, G., & Lazdunski, M.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Lazdunski, Michel
Venue
Nature Neuroscience
Published
1999-05
Volume
2
Issue
5
Pages
422-426
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W1541419413
Cited by
655
References
24
Citations by year
2026: 10 · 2025: 11 · 2024: 12 · 2023: 16 · 2022: 17 · 2021: 23 · 2020: 18 · 2019: 27 · 2018: 20 · 2017: 26 · 2016: 16 · 2015: 23 · 2014: 37 · 2013: 26 · 2012: 22
FWCI
10.34
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords
inhalational anesthetics, volatile anesthetics, two-pore domain potassium channels, tasks, TREK-1, general anesthesia, carboxy-terminal region, halothane, isoflurane, chloroform, diethyl ether, neuronal hyperpolarization
MeSH terms
Amino Acid Sequence, Animals, Lymnaea, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Potassium Channels, Porosity, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Patch-Clamp Techniques, Anesthetics, Inhalation, COS Cells, Potassium Channels, Tandem Pore Domain

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