P2X Receptors and Their Roles in Astroglia in the Central and Peripheral Nervous System
P2X Receptors and Their Roles in Astroglia in the Central and Peripheral Nervous System
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DOI：
10.1177/1073858411418524
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发表时间：
2012-10-01
期刊：
影响因子：
5.6
通讯作者：
Franke, Heike
中科院分区：
文献类型：
--
作者：
Illes, Peter;Verkhratsky, Alexei;Franke, Heike
星形胶质细胞是一类控制中枢和外周神经系统各级稳态的神经细胞。神经元-神经胶质细胞通过许多细胞外信号分子相互作用，其中最广泛的是谷氨酸和ATP。ATP激活亲离子型P2 X和亲代谢型P2 Y受体，其在神经元和星形胶质细胞中起作用。形态学、生物化学和功能证据表明星形胶质细胞P2 X（1/5）异聚体和P2 X（7）同源体受体的表达，其介导生理和病理生理反应。P2 X（1/5）受体的激活触发细胞内Na+的快速增加，其引发立即的细胞反应，例如抑制谷氨酸转运蛋白以保持突触间隙中的高谷氨酸浓度，激活局部乳酸穿梭以向突触前和突触后神经元结构提供能量底物，以及逆转Na+/Ca 2+交换导致额外的Ca 2+进入。P2 X（7）受体激活的结果主要但不完全由Ca 2+的进入介导，并导致细胞骨架的重组、炎症、凋亡/坏死和增殖，通常在延长的时间尺度上。因此，星形胶质细胞通过P2 X（1/5）和P2 X（7）受体检测从突触前神经末梢分泌的ATP的生理浓度以及在病理条件下获得的高得多的ATP浓度。
Astrocytes are a class of neural cells that control homeostasis at all levels of the central and peripheral nervous system. There is a bidirectional neuron-glia interaction via a number of extracellular signaling molecules, glutamate and ATP being the most widespread. ATP activates ionotropic P2X and metabotropic P2Y receptors, which operate in both neurons and astrocytes. Morphological, biochemical, and functional evidence indicates the expression of astroglial P2X(1/5) heteromeric and P2X(7) homomeric receptors, which mediate physiological and pathophysiological responses. Activation of P2X(1/5) receptors triggers rapid increase of intracellular Na+ that initiates immediate cellular reactions, such as the depression of the glutamate transporter to keep high glutamate concentrations in the synaptic cleft, the activation of the local lactate shuttle to supply energy substrate to pre- and postsynaptic neuronal structures, and the reversal of the Na+/Ca2+ exchange resulting in additional Ca2+ entry. The consequences of P2X(7) receptor activation are mostly but not exclusively mediated by the entry of Ca2+ and result in reorganization of the cytoskeleton, inflammation, apoptosis/necrosis, and proliferation, usually at a prolonged time scale. Thus, astroglia detect by P2X(1/5) and P2X(7) receptors both physiological concentrations of ATP secreted from presynaptic nerve terminals and also much higher concentrations of ATP attained under pathological conditions.