Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Semin Cell Dev Biol. 2011 Apr;22(2):205-13. doi: 10.1016/j.semcdb.2011.02.023. Epub 2011 Mar 3.
Astrocytes are ideally situated to integrate glial and neuronal functions and neurovascular coupling by way of their multiple contacts with neurons, glia and blood vessels. There is a high degree of specialisation of astroglial membranes at the different sites of contact, including the expression of neurotransmitter receptors, ion channels, transporters and gap junctional proteins. An apparently universal property of astrocytes throughout the CNS is their responsiveness to ATP acting via metabotropic P2Y receptors, with a prominent role for the P2Y1 receptor subtype. Activation of astroglial P2Y receptors triggers a rise in intracellular calcium, which is the substrate for astroglial excitability and intercellular communication. In addition, astrocytes have a number of mechanisms for the release of ATP, which can be considered a 'gliotransmitter'. Astrocytes may be the most widespread source of ATP release in the CNS, and astroglial ATP and its metabolite adenosine activate purine receptors on neurons, microglia, oligodendrocytes and blood vessels. There is compelling evidence that astroglial ATP and adenosine regulate neuronal synaptic strength, although the physiological significance of this astrocyte-to-neuron signalling is questioned. A less appreciated aspect of astrocyte signalling is that they also release neurotransmitters onto other glia. Notably, both ATP and adenosine control microglial behaviour and regulate oligodendrocyte differentiation and myelination. P2 receptors also mediate injury responses in all glial cell types, with a prominent role for the P2X7 receptor subtype. In addition, ATP is a potent vasoconstrictor and astrocytes provide a route for coupling blood flow to neuronal activity by way of their synaptic and perivascular connections. Thus, astrocytes are the fulcrum of neuron-glial-vascular networks and purinergic signalling is the primary mechanism by which astrocytes can integrate the functions of these diverse elements.
星形胶质细胞通过与神经元、胶质细胞和血管的多种接触，处于整合神经胶质和神经元功能以及神经血管偶联的理想位置。星形胶质细胞膜在不同的接触部位具有高度的特化，包括神经递质受体、离子通道、转运体和缝隙连接蛋白的表达。星形胶质细胞在中枢神经系统中具有一个明显的普遍特性，即对通过代谢型 P2Y 受体起作用的 ATP 作出反应，其中 P2Y1 受体亚型起着突出的作用。星形胶质细胞 P2Y 受体的激活触发细胞内钙离子的升高，这是星形胶质细胞兴奋性和细胞间通讯的基础。此外，星形胶质细胞具有许多释放 ATP 的机制，可以将其视为“神经胶质递质”。星形胶质细胞可能是中枢神经系统中 ATP 释放的最广泛来源，星形胶质细胞 ATP 及其代谢物腺苷激活神经元、小胶质细胞、少突胶质细胞和血管上的嘌呤受体。有令人信服的证据表明，星形胶质细胞 ATP 和腺苷调节神经元突触强度，尽管这种星形胶质细胞到神经元信号传递的生理意义受到质疑。星形胶质细胞信号传递的一个不太被重视的方面是，它们还将神经递质释放到其他胶质细胞上。值得注意的是，ATP 和腺苷都控制小胶质细胞的行为，并调节少突胶质细胞的分化和髓鞘形成。P2 受体也介导所有神经胶质细胞类型的损伤反应，其中 P2X7 受体亚型起着突出的作用。此外，ATP 是一种有效的血管收缩剂，星形胶质细胞通过其突触和血管周围连接为将血流与神经元活动耦合提供了途径。因此，星形胶质细胞是神经元-神经胶质-血管网络的支点，嘌呤能信号是星形胶质细胞整合这些不同元素功能的主要机制。
