Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; email:
Leicester Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 7RH, United Kingdom.
Annu Rev Physiol. 2019 Feb 10;81:43-62. doi: 10.1146/annurev-physiol-020518-114259. Epub 2018 Oct 24.
In the nervous system, ATP is co-stored in vesicles with classical transmitters and released in a regulated manner. ATP from the intracellular compartment can also exit the cell through hemichannels and following shear stress or membrane damage. In the past 30 years, the action of ATP as an extracellular transmitter at cell-surface receptors has evolved from somewhat of a novelty that was treated with skepticism to purinergic transmission being accepted as having widespread important functional roles mediated by ATP-gated ionotropic P2X receptors (P2XRs). This review focuses on work published in the last five years and provides an overview of ( a) structural studies, ( b) the molecular basis of channel properties and regulation of P2XRs, and ( c) the physiological and pathophysiological roles of ATP acting at defined P2XR subtypes.
在神经系统中,ATP 与经典递质一起储存在小泡中,并以受调控的方式释放。细胞内隔室中的 ATP 也可以通过连接小体并在切应力或膜损伤后离开细胞。在过去的 30 年中,作为细胞表面受体的细胞外递质的 ATP 作用已从最初受到怀疑的新颖观点演变为嘌呤能传递被广泛接受的观点,认为其通过 ATP 门控离子型 P2X 受体(P2XRs)介导具有广泛的重要功能作用。这篇综述重点介绍了过去五年发表的工作,并概述了(a)结构研究,(b)P2XR 通道特性和调节的分子基础,以及(c)在定义的 P2XR 亚型上发挥作用的 ATP 的生理和病理生理作用。