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 Ca²⁺-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 Ca²⁺-activated anion channel, Bestrophin-1 (Best1) by Ca²⁺ dependent mechanism through the channel pore. We demonstrate that upon activation of protease activated receptor 1 (PAR1), an increase in intracellular Ca²⁺ 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.