Receptor-mediated glutamate release from volume sensitive channels in astrocytes.
Several lines of work have shown that astrocytes release glutamate in response to receptor activation, which results in a modulation of local synaptic activity. Astrocytic glutamate release is Ca(2+)-dependent and occurs in conjunction with exocytosis of glutamate containing vesicles. However, astrocytes contain a millimolar concentration of cytosolic glutamate and express channels permeable to small anions, such as glutamate. Here, we tested the idea that astrocytes respond to receptor stimulation by dynamic changes in cell volume, resulting in volume-sensitive channel activation, and efflux of cytosolic glutamate. Confocal imaging and whole-cell recordings demonstrated that astrocytes exhibited a transient Ca(2+)-dependent cell volume increase, which activated glutamate permeable channels. HPLC analysis revealed that glutamate was released in conjunction with other amino acid osmolytes. Our observations indicate that volume-sensitive channel may constitute a previously uncharacterized target for modulation of astrocyte-neuronal interactions.
Takano
Takahiro
T
Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Kang
Jian
J
Jaiswal
Jyoti K
JK
Simon
Sanford M
SM
Lin
Jane H-C
JH
Yu
Yufei
Y
Li
Yuxing
Y
Yang
Jay
J
Dienel
Gerald
G
Zielke
H Ronald
HR
Nedergaard
Maiken
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D018031:Connexin 43 / Q000502:physiology; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology
D018031:Connexin 43; D007473:Ion Channels; D018048:Receptors, Purinergic P2; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium