OVERVIEW Exocytosis in Astrocytes: Transmitter Release and Membrane Signal Regulation Alenka Guc ˇek • Nina Vardjan • Robert Zorec Received: 1 February 2012 / Revised: 28 March 2012 / Accepted: 29 March 2012 Ó Springer Science+Business Media, LLC 2012 Abstract Astrocytes, a type of glial cells in the brain, are eukaryotic cells, and a hallmark of these are subcellular organelles, such as secretory vesicles. In neurons vesicles play a key role in signaling. Upon a stimulus—an increase in cytosolic concentration of free Ca 2? ([Ca 2? ] i )—the membrane of vesicle fuses with the presynaptic plasma membrane, allowing the exit of neurotransmitters into the extracellular space and their diffusion to the postsynaptic receptors. For decades it was thought that such vesicle- based mechanisms of gliotransmitter release were not present in astrocytes. However, in the last 30 years experimental evidence showed that astrocytes are endowed with mechanisms for vesicle- and non-vesicle-based glio- transmitter release mechanisms. The aim of this review is to focus on exocytosis, which may play a role in glio- transmission and also in other forms of cell-to-cell com- munication, such as the delivery of transporters, ion channels and antigen presenting molecules to the cell surface. Keywords Astrocytes Á Exocytosis Á Vesicle dynamics Á Gliotransmitter Á Membrane signals Introduction The term ‘‘glia’’ was coined in the middle of nineteenth century by Rudolf Virchow for cells surrounding neurons. About 30 years ago it was shown that astrocytes, the most abundant glial cell type, exhibit a special form of cyto- plasmic excitability (reviewed in [1, 2]). They respond to neurotransmitters, such as glutamate, by increasing intra- cellular Ca 2? concentration ([Ca 2? ] i ), which was first measured by optical fluorescent probes [3]. This form of astrocytic excitability provides the ability to ‘‘sense’’ glutamatergic synaptic transmission [4]. This was followed by the discovery that astrocytic Ca 2? dynamics can yield astrocyte-neuron signaling, with at least two underlying mechanisms: direct, perhaps using gap junctions [5]; and indirect utilizing glutamate released from astrocytes via Ca 2? -dependent exocytosis [6]. The later mode of signal- ing has led to the discovery of gliotransmission-based modulation of synaptic transmission [7]. However, the exact mechanisms of gliotransmitter release are a matter of debate among gliologists. Several mechanisms appear to coexist in a single astrocyte (reviewed in [8, 9]). In addition to a number of nonvesicle-based mechanisms such as (i) channel opening induced by cell swelling, (ii) release through connexin hemichannels and pannexons on the cell surface and (iii) release through ionotropic purinergic receptors, (iv) through transporters, by means of reversal uptake by plasma membrane excitatory amino acid transporters, (v) by exchange via the cystine-glutamate antiporter and organic anion transporters, glial cells release chemical Special issue: In honor of Leif Hertz. Alenka Guc ˇek, Nina Vardjan contributed equally to this work. A. Guc ˇek Á N. Vardjan Á R. Zorec (&) Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, University of Ljubljana, Zalos ˇka 4, 1000 Ljubljana, Slovenia e-mail: robert.zorec@mf.uni-lj.si N. Vardjan Á R. Zorec Celica Biomedical Center, Tehnolos ˇki park 24, 1000 Ljubljana, Slovenia R. Zorec IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 123 Neurochem Res DOI 10.1007/s11064-012-0773-6