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TREK‐1, a K + channel involved in neuroprotection and general anesthesia
Author(s) -
Heurteaux C,
Guy N,
Laigle C,
Blondeau N,
Duprat F,
Mazzuca M,
LangLazdunski L,
Widmann C,
Zanzouri M,
Romey G,
Lazdunski M
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600234
Subject(s) - neuroprotection , biology , potassium channel , polyunsaturated fatty acid , pharmacology , anesthetic , intracellular , neuroscience , biochemistry , anesthesia , endocrinology , medicine , fatty acid
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.