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TREK-1, a K+ channel involved in neuroprotection and general anesthesia
被引:413
作者:
Heurteaux, C
[1
]
Guy, N
[1
]
Laigle, C
[1
]
Blondeau, N
[1
]
Duprat, F
[1
]
Mazzuca, M
[1
]
Lang-Lazdunski, L
[1
]
Widmann, C
[1
]
Zanzouri, M
[1
]
Romey, G
[1
]
Lazdunski, M
[1
]
机构:
[1] Inst Paul Hamel, CNRS, UMR 6097, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France
关键词:
epilepsy;
ischemia;
neuroprotection;
2P domain K+ channel;
volatile anesthetics;
D O I:
10.1038/sj.emboj.7600234
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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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页码:2684 / 2695
页数:12
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