Kiss-and-run glutamate secretion in cultured and freshly isolated rat hippocampal astrocytes

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, and D-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 (similar to 2 ms) opening of the fusion pore. We conclude that, after physiological stimulation, astrocytes release glutamate via a vesicular kiss-and-run mechanism.