Inhalational anesthetics activate two-pore-domain background K+ channels
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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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
- DOI
- 10.1038/8084
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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