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

Abstract

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. 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. These results provide strong molecular evidence for potential astrocyte-neuron interaction via Best1-mediated glutamate release.