权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on dynamic regulation of synaptic transmission by glial ATP

胶质细胞ATP动态调控突触传递的研究

基本信息

批准号：
15500274
负责人：
KOIZUMI Schuichi
金额：
$ 2.43万
依托单位：
National Institute of Health Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca^<2+> transients in astrocytes and Ca^<2+> transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bi-directional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca^<2+> signaling among astrocytes, also mediates intercellular signaling between astrocytes and neurons in hippocampal cultures. Mechanical stimulation of astrocytes evoked Ca^<2+> waves mediated by the release of ATP and activation of P2 receptors. Mechanically evoked Ca^<2+> waves led to decreased excitatory glutamatergic synaptic transmission in an ATP-dependent manner. Exogenous application of ATP does not affect post-synaptic glutamatergic responses but decreased pre-synaptic exocytotic events. Finally, we show that astrocytes exhibit spontaneous Ca^<2+> oscillations mediated by extracellular ATP and that inhibition of these Ca^<2+> responses enhanced excitatory glutamatergic transmission. We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via pre-synaptic mechanisms.

星形胶质细胞最初被认为在中枢神经系统中扮演被动角色，现在已知其在突触传递的调节中具有主动作用。神经元活动可以引起星形胶质细胞中的Ca ^<2 +>瞬变，星形胶质细胞中的Ca ^<2 +>瞬变可以引起神经元活动的变化。兴奋性神经递质谷氨酸已被证明介导星形胶质细胞和神经元之间的这种双向通信。我们在此证明，ATP是星形胶质细胞间Ca ^2+信号传导的主要介质，它也在海马培养物中介导星形胶质细胞和神经元之间的细胞间信号传导。机械刺激星形胶质细胞可诱发由ATP释放和P2受体激活介导的Ca ^<2 +>波。机械诱发的Ca ^<2 +>波以ATP依赖的方式导致兴奋性突触传递的减少。外源性ATP的应用不影响突触后神经元的反应，但减少突触前的胞吐事件。最后，我们发现星形胶质细胞表现出由细胞外ATP介导的自发性Ca ^2+振荡，抑制这些Ca ^2+反应可增强兴奋性ATP能传递。因此，我们得出结论，从星形胶质细胞释放的ATP通过突触前机制发挥紧张性和活动依赖性的突触传递下调。