Neuromodulation by extracellular ATP and P2X receptors in the CNS.

Neuromodulation by extracellular ATP and P2X receptors in the CNS.
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DOI:
10.1016/j.neuron.2012.09.024
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发表时间:
2012-10-04
期刊:
影响因子:
16.2
通讯作者:
North RA
North RA
中科院分区:
医学1区
文献类型:
--
作者:
Khakh BS;North RA

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细胞外腺苷5'三磷酸(ATP)是脑中广泛存在的细胞间信号传导分子,在脑中它激活细胞表面P2X和P2Y受体。P2X受体定义了一个蛋白质家族,在序列、亚基拓扑结构、组装和结构方面不同于其他神经递质门控离子通道。在结合ATP的几毫秒内,它们催化阳离子选择性孔的打开。然而,最近的数据表明,P2X受体往往是神经调节反应的基础,时间尺度较慢,为秒或更长。在此,我们从分子、细胞和系统水平对这些发现进行综述。我们认为,虽然P2X受体是快速配体门控阳离子通道,但它们最擅长介导比CNS中快速ATP突触传递更广泛和更生理利用的缓慢神经调节功能。
Extracellular adenosine 5’ triphosphate (ATP) is a widespread cell-to-cell signaling molecule in the brain, where it activates cell surface P2X and P2Y receptors. P2X receptors define a protein family unlike other neurotransmitter-gated ion channels in terms of sequence, subunit topology, assembly and architecture. Within milliseconds of binding ATP, they catalyze the opening of a cation-selective pore. However, recent data show that P2X receptors often underlie neuromodulatory responses on slower time scales of seconds or longer. Herein, we review these findings at molecular, cellular and systems levels. We propose that, while P2X receptors are fast ligand-gated cation channels, they are most adept at mediating slow neuromodulatory functions that are more widespread and more physiologically utilized than fast ATP synaptic transmission in the CNS.
DOI: 10.1111/j.1460-9568.2011.07763.x
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