Astrocytic ATP Release

Abstract

For all its complexity, the brain can be broadly divided into two major types of cells, neurons and glial cells. Glia are defined as nonneuronal cells and function to maintain homeostasis, form myelin, and provide support and protection for neurons. Formerly thought to be passive support cells, we now know that astrocytes, the major subtype of glial cell in the brain, participate in signaling activities both with the vasculature and with neurons at the synapse. We have long known that astrocytes regulate neuronal signaling by controlling the ionic environment of the neuropil and controlling the supply of neurotransmitters to synapses, and evidence now exists for astrocytes directly signaling to neurons via regulated exocytic release, as well as signaling via gap junction mediated communication. The first indication of astrocytes actively signaling was via release of glutamate which acted to produce calcium signals in nearby neurons. Since this time astrocytes have also been shown to release d-serine, TNF-alpha, ANP, and ATP. ATP and its metabolites are well known as important signaling molecules in the nervous system, and astrocytes may be the most widespread source of ATP release in the nervous system. Astrocytes express the machinery necessary for exocytic and gap junction mediated release of ATP, as well as purinergic receptors and associated signaling molecules. In vivo studies using molecular and genetic tools have also demonstrated that astrocytic release of ATP and other signaling molecules has a major impact on synaptic transmission in multiple brain regions and under different physiological contexts. Via these actions, astrocytes have now been shown to mediate complex functions in the whole organism, such as respiration and homeostatic control of the sleep–wake cycle.