Under physiological conditions, astrocytes not only passively support and nourish adjacent neurons, but also actively modulate neuronal transmission by releasing “glial transmitters,” such as glutamate, ATP, andd-serine. Unlike the case for neurons, the mechanisms by which glia release transmitters are essentially unknown. Here, by using electrochemical amperometry and frequency-modulated single-vesicle imaging, we discovered that hippocampal astrocytes exhibit two modes of exocytosis of glutamate in response to various stimuli. After physiological stimulation, a glial vesicle releases a quantal content that is only 10% of that induced by nonphysiological, mechanical stimulation. The small release event arises from a brief (∼2 ms) opening of the fusion pore. We conclude that, after physiological stimulation, astrocytes release glutamate via a vesicular “kiss-and-run” mechanism.
