Nonsynaptic and nonvesicular ATP release from neurons and relevance to neuron–glia signaling

Abstract

Studies on the release of ATP from neurons began with the earliest investigations of quantal neurotransmitter release in the 1950s, but in contrast to ATP release from other cells, studies of ATP release from neurons have been narrowly constrained to one mechanism, vesicular release. This is a consequence of the prominence of synaptic transmission in neuronal communication, but nonvesicular mechanisms for ATP release from neurons are likely to have a broader range of functions than synaptic release. Investigations of activity-dependent communication between axons and myelinating glia have stimulated a search for mechanisms that could release ATP from axons and other nonsynaptic regions in response to action potential firing. This has identified volume-activated anion channels as an important mechanism in activity-dependent ATP release from axons, and renewed interest in micromechanical changes in axons that accompany action potential firing.

The Interaction between Cell Adhesion Molecule L1, Matrix Metalloproteinase 14, and Adenine Nucleotide Translocator at the Plasma Membrane Regulates L1-Mediated Neurite Outgrowth of Murine Cerebellar Neurons

“…Here, we showed that stimulation of L1 signaling also triggers tyrosine phosphorylation of ANT1, ANT2, and MMP14 and reduces intracellular ATP levels, being associated with transient ANT-dependent release of ATP (Fig. 10 B), which could act as a neurotransmitter or extracellularly phosphorylate neuritogenic molecules (Fields, 2011;Lalo et al, 2011) (Fig. 10 B).…”

Intracellular and Extracellular ATP Coordinately Regulate the Inverse Correlation between Osteoclast Survival and Bone Resorption

“…The mechanism of nucleotide release from cells is currently not sufficiently understood. Recently, several mechanisms for ATP release from cells have been proposed, and they are activated by a wide range of stimuli (52,53). These ATP release mechanisms include damage to the cell membrane, mechanical stress, hypoxia, inflammation, several agonists, and electrical excitation of neural tissue.…”

Protecting White Matter From Stroke Injury

“…67 Astrocytes and oligodendrocytes express all 4 subtypes of P1 receptors and their activation induces Ca 2+ release from internal stores in both cell types, and regulates oligodendrocyte maturation and myelination. 68 Moreover, central axonal conduction may be modulated by adenosine because blockade of A1 receptors in axon shafts also increases the width of action potentials. 60 ATP signaling in WM astrocytes and oligodendrocytes occurs through a variety of P2X receptors, which are highly Ca 2+ permeable, and P2Y receptors, which mobilize Ca 2+ from intracellular stores.…”

“…12,77 Thus, oligodendrocytes can be partially protected from irreversible ischemic injury, including perinatal ischemia, by glutamate receptor antagonists and glutamate uptake inhibitors 11,[16][17][18][19][20] (Table; Figure 3; refs. 44,68). In models of developing WM, simulated ischemia induces an inward current in oligodendrocytes that is mediated, in part, by NMDA and AMPA/kainate receptors, 19 and increases Ca 2+ levels in myelin itself (an effect Figure 3.…”