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.


RESULTS
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.
Korea Institute of Science and Technology, Seoul, South Korea.
Soo-Jin
SJ
Oh
Kyung-Seok
KS
Han
Hyungju
H
Park
Dong Ho
DH
Woo
Hye Yun
HY
Kim
Stephen F
SF
Traynelis
C Justin
CJ
Lee
D000818:Animals; D000838:Anions; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D000075002:Bestrophins; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D005136:Eye Proteins / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D018698:Glutamic Acid / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000378:metabolism*
D000838:Anions; C491856:Best1 protein, mouse; D000075002:Bestrophins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005136:Eye Proteins; D007473:Ion Channels; D009842:Oligopeptides; C462999:PAR-1-activating peptide; D044463:Receptor, PAR-1; D018698:Glutamic Acid