Trends in Neurosciences
Volume 23, Issue 12, 1 December 2000, Pages 625-633
Journal home page for Trends in Neurosciences

Review
ATP: an extracellular signaling molecule between neurons and glia

https://doi.org/10.1016/S0166-2236(00)01674-XGet rights and content

Abstract

Recent studies on Schwann cells at the neuromuscular junction and non-synaptic regions of premyelinated axons indicate that extracellular ATP can act as an activity-dependent signaling molecule in communication between neurons and glia. Several mechanisms have been observed for the regulated release of ATP from synaptic and non-synaptic regions, and a diverse family of receptors for extracellular ATP has been characterized. The findings suggest functional consequences of neuron–glial communication beyond homeostasis of the extracellular environment surrounding neurons, including regulating synaptic strength, gene expression, mitotic rate, and differentiation of glia according to impulse activity in neural circuits.

Section snippets

Glial receptors for the vesicular release of neurotransmitters

Astrocytes in the CNS and Schwann cells in the PNS surround synaptic junctions and help maintain the extracellular environment by providing physical integrity, and regulating the extracellular ion and neuro-transmitter concentration. Ca2+ imaging, molecular, and electrophysiological methods show that, under appropriate conditions, oligodendrocyte precursor cells (OPC), astrocytes and Schwann cells can detect the vesicular release of neurotransmitters. The stimulated glia can subsequently

Extrasynaptic neuron–glial signaling

Activity-dependent interactions between neurons and glia in extrasynaptic regions would encompass a large range of functions, including myelination and various glial functions unrelated to synaptic transmission (e.g. proliferation and differentiation). Time-lapse confocal microscopy has recently shown that Schwann cells in culture can respond to electrical stimulation of premyelinated DRG axons2 (Fig. 1). This is particularly interesting because these neurons lack synapses and nodes of Ranvier

ATP release in neurotrauma

Cellular damage can release large amounts of ATP into the extracellular environment because the internal concentration of ATP can be between 3–5 mm (Refs 29., 34.). Such ATP release might be important in triggering cellular responses to trauma and ischemia, by initiating and maintaining reactive astrogliosis, which involves striking changes in astrocyte proliferation and morphology54., 61.. Nucleosides and nucleotides that are released from dying cells also stimulate proliferation of microglia

Directions for future research

Research on the glial cell of the PNS has shown that extracellular ATP is an important molecule in activity-dependent signaling between neurons and glia at the synapse and in non-synaptic regions. Research on glia of the CNS has shown the importance of ATP in astrocyte–astrocyte signaling and of neural impulse activity in regulating glial functions by the vesicular release of neurotransmitters. A future research area will be to determine whether ATP might also mediate neuron–glial signaling in

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