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5'-三磷酸腺苷敏感性钾通道

Adenosine 5'-triphosphate-sensitive potassium channels.

作者信息

Ashcroft F M

机构信息

University Laboratory of Physiology, Oxford, England.

出版信息

Annu Rev Neurosci. 1988;11:97-118. doi: 10.1146/annurev.ne.11.030188.000525.

Abstract

This review has focused on the properties of the ATP-sensitive K-channel found in cardiac and skeletal muscle, and in pancreatic beta-cells. It is conceivable that this channel will be found in other cell types. In particular, it would be worthwhile looking for its presence in those cells in which electrical activity is linked to metabolism, glucose concentration, or oxygen levels. Obvious examples are the glucoreceptor neurons of mammalian brain and chemoreceptors such as those of the carotid body. While ATP-sensitive K-channels in cardiac and skeletal muscle membranes are rather similar, there are a few significant differences between these channels and that found in the beta-cell. Most notably, the latter is more sensitive to inhibition by ATP and sulphonylureas. It remains to be seen whether they also differ in the ability of nucleotides to activate the channel. Considerable confusion also still surrounds the physiological regulation of the ATP-sensitive K-channel in intact cells. Although the general consensus seems to be that [ATP]i modulates channel activity, the role of other nucleotides and ions as well as the way in which their concentrations alter with metabolism requires further elucidation. A combined electrophysiological and biochemical approach is likely to prove most successful in establishing which second messenger systems contribute to the physiological regulation of the ATP-sensitive K-channel. Finally, the close correlation between cell metabolism and the activity of the ATP-sensitive K-channel raises the intriguing possibility that disorders of cell metabolism might produce alterations in channel activity and consequent changes in cell function.

摘要

本综述聚焦于在心肌、骨骼肌以及胰腺β细胞中发现的ATP敏感性钾通道的特性。可以想象,这种通道可能存在于其他细胞类型中。特别是,值得去寻找它在那些电活动与代谢、葡萄糖浓度或氧水平相关的细胞中的存在情况。明显的例子有哺乳动物大脑中的葡萄糖受体神经元以及诸如颈动脉体中的化学感受器。虽然心肌和骨骼肌膜中的ATP敏感性钾通道颇为相似,但这些通道与β细胞中的通道存在一些显著差异。最显著的是,后者对ATP和磺酰脲类药物的抑制更为敏感。它们在核苷酸激活通道的能力方面是否也存在差异还有待观察。完整细胞中ATP敏感性钾通道的生理调节也仍然存在相当大的困惑。尽管普遍的共识似乎是细胞内ATP浓度([ATP]i)调节通道活性,但其他核苷酸和离子的作用以及它们的浓度随代谢如何变化仍需进一步阐明。在确定哪些第二信使系统对ATP敏感性钾通道的生理调节有贡献方面,结合电生理学和生物化学的方法可能最为成功。最后,细胞代谢与ATP敏感性钾通道活性之间的密切关联引发了一个有趣的可能性,即细胞代谢紊乱可能导致通道活性改变,进而引起细胞功能变化。

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