Vesicular release of ATP at central synapses

Adenosine triphosphate (ATP) acts as a fast excitatory transmitter in several regions of the central nervous system (CNS) including the medial habenula, dorsal horn, locus coeruleus, hippocampus, and somatosensory cortex. Postsynaptic actions of ATP are mediated through an extended family of P2X receptors, widely expressed throughout the CNS. ATP is released via several pathways, including exocytosis from presynaptic terminals and diffusion through large transmembrane pores (e.g., hemichannels, P2X7 receptors, or volume-sensitive chloride channels) expressed in astroglial membranes. In presynaptic terminals, ATP is accumulated and stored in the synaptic vesicles. In different presynaptic terminals, these vesicles may contain ATP only or ATP and another neurotransmitter [e.g., γ-amino-butyric acid (GABA) or glutamate]; in the latter case, two transmitters can be coreleased. Here, we discuss the mechanisms of vesicular release of ATP in the CNS and present our own data, which indicate that in central neuronal terminals, ATP is primarily stored and released from distinct pool of vesicles; the release of ATP is not synchronized either with GABA or with glutamate.