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.
引用
收藏
页码:2684 / 2695
页数:12
相关论文
共 54 条
[41]   DETERMINATION AND APPLICATIONS OF MAC [J].
QUASHA, AL ;
EGER, EI ;
TINKER, JH .
ANESTHESIOLOGY, 1980, 53 (04) :315-334
[42]   AN ESSENTIAL SET OF K(+) CHANNELS CONSERVED IN FLIES, MICE AND HUMANS [J].
SALKOFF, L ;
BAKER, K ;
BUTLER, A ;
COVARRUBIAS, M ;
PAK, MD ;
WEI, AG .
TRENDS IN NEUROSCIENCES, 1992, 15 (05) :161-166
[43]   Characterization of a recovery global cerebral ischemia model in the mouse [J].
Sheng, HX ;
Laskowitz, DT ;
Pearlstein, RD ;
Warner, DS .
JOURNAL OF NEUROSCIENCE METHODS, 1999, 88 (01) :103-109
[44]   SEROTONIN AND CYCLIC-AMP CLOSE SINGLE K+- CHANNELS IN APLYSIA SENSORY NEURONS [J].
SIEGELBAUM, SA ;
CAMARDO, JS ;
KANDEL, ER .
NATURE, 1982, 299 (5882) :413-417
[45]   FOS-LACZ TRANSGENIC MICE - MAPPING SITES OF GENE INDUCTION IN THE CENTRAL-NERVOUS-SYSTEM [J].
SMEYNE, RJ ;
SCHILLING, K ;
ROBERTSON, L ;
LUK, D ;
OBERDICK, J ;
CURRAN, T ;
MORGAN, JI .
NEURON, 1992, 8 (01) :13-23
[46]   Fish oils and bipolar disorder - A promising but untested treatment - Reply [J].
Stoll, AL ;
Marangell, LB .
ARCHIVES OF GENERAL PSYCHIATRY, 1999, 56 (05) :415-416
[47]   CNS distribution of members of the two-pore-domain (KCNK) potassium channel family [J].
Talley, EM ;
Solórzano, G ;
Lei, QB ;
Kim, D ;
Bayliss, DA .
JOURNAL OF NEUROSCIENCE, 2001, 21 (19) :7491-7505
[48]   Two-pore-domain (KCNK) potassium channels: Dynamic roles in neuronal function [J].
Talley, EM ;
Sirois, JE ;
Lei, QB ;
Bayliss, DA .
NEUROSCIENTIST, 2003, 9 (01) :46-56
[49]   GABAergic mechanisms in epilepsy [J].
Treiman, DM .
EPILEPSIA, 2001, 42 :8-12
[50]   EXCITOTOXIN-INDUCED NEURONAL DEGENERATION AND SEIZURE ARE MEDIATED BY TISSUE-PLASMINOGEN ACTIVATOR [J].
TSIRKA, SE ;
GUALANDRIS, A ;
AMARAL, DG ;
STRICKLAND, S .
NATURE, 1995, 377 (6547) :340-344