title: Receptor-mediated glutamate release from volume sensitive channels in astrocytes.
abstract: 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.
authors.affiliation: Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Jyoti K
authors.initials: JK
authors.lastname: Jaiswal
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Simon
authors.forename: Jane H-C
authors.initials: JH
authors.lastname: Lin
authors.forename: Yufei
authors.initials: Y
authors.lastname: Yu
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Li
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
authors.forename: Gerald
authors.initials: G
authors.lastname: Dienel
authors.forename: H Ronald
authors.initials: HR
authors.lastname: Zielke
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: 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
chemical_list: D018031:Connexin 43; D007473:Ion Channels; D018048:Receptors, Purinergic P2; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium