内源性大麻素花生四烯乙醇胺是背景钾离子通道TASK-1的直接且选择性阻断剂。
The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1.
作者信息
Maingret F, Patel A J, Lazdunski M, Honoré E
机构信息
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
出版信息
EMBO J. 2001 Jan 15;20(1-2):47-54. doi: 10.1093/emboj/20.1.47.
Abstract
TASK-1 encodes an acid- and anaesthetic-sensitive background K(+) current, which sets the resting membrane potential of both cerebellar granule neurons and somatic motoneurons. We demonstrate that TASK-1, unlike the other two pore (2P) domain K(+) channels, is directly blocked by submicromolar concentrations of the endocannabinoid anandamide, independently of the CB1 and CB2 receptors. In cerebellar granule neurons, anandamide also blocks the TASK-1 standing-outward K(+) current, IKso, and induces depolarization. Anandamide-induced neurobehavioural effects are only partly reversed by antagonists of the cannabinoid receptors, suggesting the involvement of alternative pathways. TASK-1 constitutes a novel sensitive molecular target for this endocannabinoid.
摘要
TASK-1编码一种对酸和麻醉敏感的背景钾离子电流，该电流设定了小脑颗粒神经元和躯体运动神经元的静息膜电位。我们证明，与其他双孔（2P）结构域钾离子通道不同，TASK-1可被亚微摩尔浓度的内源性大麻素花生四烯酸乙醇胺直接阻断，且不依赖于CB1和CB2受体。在小脑颗粒神经元中，花生四烯酸乙醇胺还可阻断TASK-1外向持续钾离子电流（IKso）并诱导去极化。大麻素受体拮抗剂只能部分逆转花生四烯酸乙醇胺诱导的神经行为效应，这表明存在其他途径参与其中。TASK-1构成了这种内源性大麻素的一个新的敏感分子靶点。
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