TREK-1, a K+ channel involved in neuroprotection and general anesthesia
Open accessAbstract
TREK-1 is a two-pore-domain background potassium channel expressed throughout the central nervous system. It is opened by polyunsaturated fatty acids and lysophospholipids. It is inhibited by neurotransmitters that produce an increase in intracellular cAMP and by those that activate the Gq protein pathway. TREK-1 is also activated by volatile anesthetics and has been suggested to be an important target in the action of these drugs. Using mice with a disrupted TREK-1 gene, we now show that TREK-1 has an important role in neuroprotection against epilepsy and brain and spinal chord ischemia. Trek1-/- mice display an increased sensitivity to ischemia and epilepsy. Neuroprotection by polyunsaturated fatty acids, which is impressive in Trek1+/+ mice, disappears in Trek1-/- mice indicating a central role of TREK-1 in this process. Trek1-/- mice are also resistant to anesthesia by volatile anesthetics. TREK-1 emerges as a potential innovative target for developing new therapeutic agents for neurology and anesthesiology.
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No single gene mutation completely removes volatile anesthetic responsiveness.
“no single gene mutation fully ablates volatile anesthetic responsiveness.”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [11]
Deletion of TREK-1 in mice causes substantial resistance to five distinct volatile anesthetics.
“Deletion of TREK-1 in mice confers substantial resistance to five distinct volatile anesthetics [11].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [11]
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- Authors
- Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang‐Lazdunski, L., Widmann, C., Zanzouri, M., Romey, G., & Lazdunski, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Lazdunski, M
- Venue
- The EMBO Journal
- Published
- 2004-06-03
- Volume
- 23
- Issue
- 13
- Pages
- 2684-2695
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC449762
- OpenAlex
- W2096104904
- Cited by
- 534
- References
- 56
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 13 · 2023: 20 · 2022: 16 · 2021: 36 · 2020: 28 · 2019: 22 · 2018: 28 · 2017: 16 · 2016: 17 · 2015: 22 · 2014: 38 · 2013: 22 · 2012: 29
- FWCI
- 10.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- TREK-1, two-pore domain potassium channels, neuroprotection, general anesthesia, volatile anesthetics, epilepsy, cerebral ischemia, spinal cord ischemia, polyunsaturated fatty acids, lysophospholipids, cAMP signaling, therapeutic target
- MeSH terms
- Cyclic AMP, Anesthesia, General, Animals, Behavior, Animal, Chlorocebus aethiops, Brain Ischemia, Epilepsy, Fatty Acids, Unsaturated, Heterozygote, Homozygote, Immunohistochemistry, Lysophospholipids, Potassium Channels, Gene Expression, Gene Deletion, Mice, Knockout, Patch-Clamp Techniques, Anesthetics, General, Neuroprotective Agents, Ischemic Preconditioning, COS Cells, Reverse Transcriptase Polymerase Chain Reaction, Spinal Cord Ischemia, Potassium Channels, Tandem Pore Domain, GTP-Binding Protein alpha Subunits, Gq-G11, Mice
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