Malchow Robert Paul, Tchernookova Boriana K, Choi Ji-In Vivien, Smith Peter J S, Kramer Richard H, Kreitzer Matthew A
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, United States.
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, United States.
Front Cell Neurosci. 2021 Sep 3;15:693095. doi: 10.3389/fncel.2021.693095. eCollection 2021.
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.
有大量证据支持神经胶质细胞能够调节神经细胞之间突触连接强度这一观点，并且进一步有人提出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传导的分子机制仍存在激烈争议。最近的实验表明，细胞外ATP引发的细胞外氢离子外流变化可能在视网膜中的放射状胶质细胞和整个大脑中的星形胶质细胞对突触强度的调节中起关键作用。利用自参考氢离子选择性微电极，首次从虎螈视网膜酶解分离出的米勒细胞中检测到ATP引发的放射状胶质细胞氢离子通量变化。进一步发现，ATP引发的氢离子外流变化在进化上具有高度保守性，延伸到从七鳃鳗、鳐鱼、大鼠、小鼠、猴子和人类等不同物种分离出的米勒细胞。最近，自参考氢离子选择性电极已被用于检测来自皮质和海马体的单个哺乳动物星形胶质细胞周围ATP引发的氢离子外流变化。与细胞内钙的增加相关，这些ATP诱导的细胞外酸化很可能是突触调节的关键介质。在本文中，我们研究了支持氢离子作为神经传递关键调节因子的证据，回顾了表明细胞外ATP引发神经胶质细胞氢离子外流增加的数据，并描述了参与神经胶质细胞介导的氢离子外流的潜在信号转导途径。然后，我们研究了神经胶质细胞释放的细胞外氢离子在调节脊椎动物视网膜内突触传递中可能发挥的潜在作用，接着将重点扩展到讨论其在扩散性抑制、偏头痛、癫痫和脑节律改变中的潜在作用，并提出细胞外氢离子的变化可能是将这些不同现象联系起来的一个统一特征。
