Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain

Nina Vardjan, Marko Kreft, Robert Zorec, Vardjan, Nina, Kreft, Marko, Zorec, Robert

It is becoming clear that astrocytes, the most abundant type of glial cells in the mammalian brain, share many properties with neurons. One such property involves vesicles, which play a key role in cell-to-cell signaling. On the one hand, vesicles determine the signaling potential by delivering various receptors and transporters to the plasma membrane by vesicular exocytosis. On the other hand, vesicles are used in astrocytes for the release of vesicle-laden chemical messengers. This chapter compares the properties of Ca(2+)-dependent fusion of the vesicle membrane with the plasma membrane in astrocytes and in neurons, monitored by membrane capacitance techniques. Moreover, we focus on membrane-bound vesicles that store gliotransmitters, glutamate, and adenosine 5'-triphosphate (ATP), to learn why regulated exocytosis in astrocytes is orders of magnitude slower than in neurons and the fact that these signaling molecules are also metabolites. The relatively slow kinetics of regulated exocytosis in astrocytes likely involves vesicle dynamics regulation and mechanisms governing the merger of the vesicle membrane with the plasma membrane, but may also depend on the availability of ATP and glutamate in metabolic pathways for packaging into vesicles via specific vesicle transporters.