BK 通道：酒精耐受的介质和模型。
BK Channels: mediators and models for alcohol tolerance.
机构信息
Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan 00901, Puerto Rico.
出版信息
Trends Neurosci. 2009 Dec;32(12):629-37. doi: 10.1016/j.tins.2009.08.001. Epub 2009 Sep 24.
Abstract
Enhanced acute tolerance predicts alcohol abuse. We describe work on the role of the calcium- and voltage-gated BK channel in alcohol tolerance, highlighting the lipid environment, BK protein isoform selection and auxiliary BK channel proteins. We show how ethanol, which had the reputation of a nonspecific membrane perturbant, is now being examined at realistic concentrations with cutting-edge techniques, providing novel molecular targets for therapeutic approaches to alcoholism. Addictive disorders impact our emotional, physical and financial status, and burden our healthcare system. Although alcohol is the focus of this review, it is highly probable, given the common neural and biochemical pathways used by drugs of abuse, that the findings described here will also apply to other drugs.
摘要
增强的急性耐受预示着酒精滥用。我们描述了钙和电压门控 BK 通道在酒精耐受中的作用，重点介绍了脂质环境、BK 蛋白同工型选择和辅助 BK 通道蛋白。我们展示了乙醇，这种曾被认为是非特异性膜扰动剂的物质，现在正以现实浓度结合尖端技术进行研究，为治疗酗酒的方法提供了新的分子靶点。成瘾性疾病影响我们的情绪、身体和财务状况，并给我们的医疗系统带来负担。虽然本文的重点是酒精，但鉴于滥用药物使用的共同神经和生化途径，很有可能这里描述的发现也适用于其他药物。
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本文引用的文献
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Sizing up ethanol-induced plasticity: the role of small and large conductance calcium-activated potassium channels.评估乙醇诱导的可塑性：小电导和大电导钙激活钾通道的作用。
Alcohol Clin Exp Res. 2009 Jul;33(7):1125-35. doi: 10.1111/j.1530-0277.2009.00936.x. Epub 2009 Apr 9.
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Molecular mechanisms of BK channel activation.BK通道激活的分子机制。
Cell Mol Life Sci. 2009 Mar;66(5):852-75. doi: 10.1007/s00018-008-8609-x.
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BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.BK通道调节视交叉上核中的自发动作电位节律。
PLoS One. 2008;3(12):e3884. doi: 10.1371/journal.pone.0003884. Epub 2008 Dec 8.
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Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol.鉴定一种控制对酒精的分子和行为耐受性的BK通道辅助蛋白。
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The BK-mediated fAHP is modulated by learning a hippocampus-dependent task.BK介导的迟发性外向电流通过学习海马依赖性任务受到调节。
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15154-9. doi: 10.1073/pnas.0805855105. Epub 2008 Sep 17.
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Large-conductance calcium-dependent potassium channels prevent dendritic excitability in neocortical pyramidal neurons.大电导钙依赖性钾通道可防止新皮层锥体神经元的树突兴奋性。
Pflugers Arch. 2009 Mar;457(5):1133-45. doi: 10.1007/s00424-008-0569-3. Epub 2008 Sep 2.
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Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol.miR-9对BK通道剪接变体稳定性的转录后调控是神经对酒精适应的基础。
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