Protease activated receptor 1-induced glutamate release in cultured astrocytes is mediated by Bestrophin-1 channel but not by vesicular exocytosis

BACKGROUND: Glutamate is the major transmitter that mediates the principal form of excitatory synaptic transmission in the brain. It has been well established that glutamate is released via Ca(2+)-dependent exocytosis of glutamate-containing vesicles in neurons. However, whether astrocytes exocytose to release glutamate under physiological condition is still unclear. FINDINGS: We report a novel form of glutamate release in astrocytes via the recently characterized Ca(2+)-activated anion channel, Bestrophin-1 (Best1) by Ca(2+) dependent mechanism through the channel pore. We demonstrate that upon activation of protease activated receptor 1 (PAR1), an increase in intracellular Ca(2+) concentration leads to an opening of Best1 channels and subsequent release of glutamate in cultured astrocytes. CONCLUSIONS: These results provide strong molecular evidence for potential astrocyte-neuron interaction via Best1-mediated glutamate release.