Abstract
Astrocytes participate in information processing by actively modulating synaptic properties via gliotransmitter release. Various mechanisms of astrocytic release have been reported, including release from storage organelles via exocytosis and release from the cytosol via plasma membrane ion channels and pumps. It is still not fully clear which mechanisms operate under which conditions, but some of them, being Ca2+-regulated, may be physiologically relevant. The properties of Ca2+-dependent transmitter release via exocytosis or via ion channels are different and expected to produce different extracellular transmitter concentrations over time and to have distinct functional consequences. The molecular aspects of these two release pathways are still under active investigation. Here, we discuss the existing morphological and functional evidence in support of either of them. Transgenic mouse models, specific antagonists and localization studies have provided insight into regulated exocytosis, albeit not in a systematic fashion. Even more remains to be uncovered about the details of channel-mediated release. Better functional tools and improved ultrastructural approaches are needed in order fully to define specific modalities and effects of astrocytic gliotransmitter release pathways.
Highlights
The importance of astrocytes in brain function is increasingly appreciated
What do we know about gliotransmitter release from astrocytes? There is clear evidence that astrocytes respond to synaptic signals with gliotransmitter release
Gliotransmission 7 has been observed with multiple experimental approaches from various independent groups [10] and cannot just be an artefact [9]
Summary
The importance of astrocytes in brain function is increasingly appreciated. In addition to providing homeostatic control and metabolic support, they play an active role in information processing within neuronal circuits [1,2]. There is no clear evidence that channel-mediated (connexins/pannexins/P2X7) mechanisms are relevant to physiological communication between astrocytes and neurons, because opening of the channels was shown to occur mainly under non-physiological conditions such as traumatic injury, seizure activity and altered oxygen and glucose concentrations [5,6]. Ca2þ-dependent exocytosis has been proposed as the major mechanism for release of the main gliotransmitters (glutamate, D-serine and ATP), similar to what happens in neurons and secretory cells. An anion channel, Bestrophin-1 (Best-1), has been reported to play a role in GABA and glutamate release from astrocytes under physiological conditions [7,8]. Whether regulated exocytosis or a channel-mediated mechanism (or both) is responsible for gliotransmission under physiological conditions presently remains a topic of active debate [3,9]. We will discuss vesicular exocytosis and Best-1 channel release because both these pathways are Ca2þ-dependent and putatively physiologically relevant
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