PDF(Pubmed)
Abstract：
There is significant evidence to support the notion that glial cells can modulate the strength of synaptic connections between nerve cells, and it has further been suggested that alterations in intracellular calcium are likely to play a key role in this process. However, the molecular mechanism(s) by which glial cells modulate neuronal signaling remains contentiously debated. Recent experiments have suggested that alterations in extracellular H+ efflux initiated by extracellular ATP may play a key role in the modulation of synaptic strength by radial glial cells in the retina and astrocytes throughout the brain. ATP-elicited alterations in H+ flux from radial glial cells were first detected from Müller cells enzymatically dissociated from the retina of tiger salamander using self-referencing H+-selective microelectrodes. The ATP-elicited alteration in H+ efflux was further found to be highly evolutionarily conserved, extending to Müller cells isolated from species as diverse as lamprey, skate, rat, mouse, monkey and human. More recently, self-referencing H+-selective electrodes have been used to detect ATP-elicited alterations in H+ efflux around individual mammalian astrocytes from the cortex and hippocampus. Tied to increases in intracellular calcium, these ATP-induced extracellular acidifications are well-positioned to be key mediators of synaptic modulation. In this article, we examine the evidence supporting H+ as a key modulator of neurotransmission, review data showing that extracellular ATP elicits an increase in H+ efflux from glial cells, and describe the potential signal transduction pathways involved in glial cell-mediated H+ efflux. We then examine the potential role that extracellular H+ released by glia might play in regulating synaptic transmission within the vertebrate retina, and then expand the focus to discuss potential roles in spreading depression, migraine, epilepsy, and alterations in brain rhythms, and suggest that alterations in extracellular H+ may be a unifying feature linking these disparate phenomena.
摘要：
有大量证据支持神经胶质细胞可以调节神经细胞之间突触连接的强度，进一步表明，细胞内钙的变化可能在这一过程中起关键作用。然而,神经胶质细胞调节神经元信号的分子机制仍有争议。最近的实验表明，由细胞外ATP引发的细胞外H外排的改变可能在整个大脑中视网膜和星形胶质细胞中的放射状神经胶质细胞调节突触强度中起关键作用。首先使用自参考H选择性微电极从虎sal的视网膜酶解离的Müller细胞中检测到ATP引起的放射状神经胶质细胞H通量的改变。进一步发现ATP引起的H外排改变在进化上是高度保守的，延伸到Müller细胞，这些细胞从各种物种中分离出来，滑冰,rat,鼠标,猴子和人类最近,自参考H选择性电极已用于检测ATP引起的皮质和海马中单个哺乳动物星形胶质细胞周围H外排的变化。与细胞内钙的增加有关，这些ATP诱导的细胞外酸化被很好地定位为突触调节的关键介质。在这篇文章中,我们研究了支持H+作为神经传递的关键调节剂的证据，回顾数据显示细胞外ATP引起神经胶质细胞的H+外排增加，并描述了神经胶质细胞介导的H外排的潜在信号转导途径。然后，我们研究了胶质细胞释放的细胞外H+在调节脊椎动物视网膜内的突触传递中可能发挥的潜在作用，然后将焦点扩展到讨论传播抑郁症的潜在作用，偏头痛,癫痫,和大脑节律的改变，并表明细胞外H的变化可能是连接这些不同现象的统一特征。
