The lipid-activated two-pore domain K+ channel TREK-1 is resistant to hypoxia:: implication for ischaemic neuroprotection
The lipid-activated two-pore domain K+ channel TREK-1 is resistant to hypoxia:: implication for ischaemic neuroprotection
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DOI：
10.1113/jphysiol.2004.077503
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发表时间：
2005-01-01
影响因子：
5.5
通讯作者：
Honoré, E
中科院分区：
文献类型：
--
作者：
Buckler, KJ;Honoré, E
TREK-1是机械、热、pH、电压和脂质敏感的双孔结构域钾（K，p）通道家族的成员。它在中枢神经系统中高度表达，可能编码先前描述的花生四烯酸激活的K+通道之一。多不饱和脂肪酸和溶血磷脂可以保护大脑免受全身缺血的影响。由于这两种脂质都是TREK-1的开放剂，因此已经表明这种K-2 P通道直接参与神经保护。然而，最近，这一观点受到了一份报告的挑战，该报告声称TREK-1及其被花生四烯酸激活的作用受到缺氧的抑制。在本研究中，我们证明，鼓泡的盐水与气体的结果在损失的花生四烯酸从溶液中。使用证实该实验假象的实验条件，我们证明TREK-I对缺氧具有抗性，并且即使在低P-O 2（< 4 Torr）下也被花生四烯酸强烈活化。此外，缺氧不能影响基础以及2，4，6-三硝基苯酚和酸刺激的TREK-1电流。这些数据支持TREK-1在缺血性神经保护和通过花生四烯酸的细胞信号传导中的可能作用。
TREK-1 is a member of the two-pore domain potassium (K,p) channel family that is mechano-, heat, pH, voltage and lipid sensitive. It is highly expressed in the central nervous system and is probably encodes one of the previously described arachidonic acid-activated K+ channels. Polyunsaturated fatty acids and lysophospholipids protect the brain against global ischaemia. Since both lipids are openers of TREK-1, it has been suggested that this K-2P channel is directly involved in neuroprotection. Recently, however, this view has been challenged by a report claiming that TREK-1 and its activation by arachidonic acid is inhibited by hypoxiia. In the present study, we demonstrate that the bubbling of saline with gases results in the loss of arachidonic acid from solution. Using experimental conditions which obviate this experimental artefact we demonstrate that TREK-I is resistant to hypoxia and is strongly activated by arachidonic acid even at low P-O2 (< 4 Torr). Furthermore, hypoxia fails to affect basal as well as 2,4,6-trinitrophenol- and acid-stimulated TREK-1 currents. These data are supportive for a possible role of TREK-1 in ischaemic neuroprotection and in cell signalling via arachidonic acid.