Glutamate down-regulates GLAST expression through AMPA receptors in Bergmann glial cells

The Na(+)-dependent glutamate/aspartate transporter GLAST plays a major role in the removal of glutamate from the synaptic cleft. Short-, as well as long-term changes in transporter activity are triggered by glutamate. An important locus of regulation is the density of transporter molecules at the plasma membrane. A substrate-dependent change in the translocation rate accounts for the short-term effect, whereas the mechanisms of long-term modulation are less understood. Using cultured chick cerebellar Bergmann glial cells, we report here that glutamate receptors mediate a substantial reduction in GLAST mRNA levels, suggesting a transcriptional level of regulation. Moreover, when the 5' proximal region of the GLAST gene was cloned and transfected into Bergmann glia cells, a decrease in promoter activity was induced by glutamate exposure. The use of specific pharmacological tools established the involvement of Ca(2+)-permeable alpha-amino 3-hydroxy-5-methyl-4-isoaxazolepropionate (AMPA) receptors via protein kinase C and c-Jun. These results demonstrate that GLAST is under transcriptional control through glutamate receptors activation, and further supports the participation of Bergmann glia cells in the modulation of glutamatergic transmission.