Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-157
Jabaudon, D; Scanziani, M; Gähwiler, B H; Gerber, U (2000). Acute decrease in net glutamate uptake during energy deprivation. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 97(10):5610-5615.
View at publisher
The extracellular glutamate concentration ([glu](o)) rises during cerebral ischemia, reaching levels capable of inducing delayed neuronal death. The mechanisms underlying this glutamate accumulation remain controversial. We used N-methyl-D-aspartate receptors on CA3 pyramidal neurons as a real-time, on-site, glutamate sensor to identify the source of glutamate release in an in vitro model of ischemia. Using glutamate and L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) as substrates and DL-threo-beta-benzyloxyaspartate (TBOA) as an inhibitor of glutamate transporters, we demonstrate that energy deprivation decreases net glutamate uptake within 2-3 min and later promotes reverse glutamate transport. This process accounts for up to 50% of the glutamate accumulation during energy deprivation. Enhanced action potential-independent vesicular release also contributes to the increase in [glu](o), by approximately 50%, but only once glutamate uptake is inhibited. These results indicate that a significant rise in [glu](o) already occurs during the first minutes of energy deprivation and is the consequence of reduced uptake and increased vesicular and nonvesicular release of glutamate.
51 downloads since deposited on 11 Feb 2008
7 downloads since 12 months
|Item Type:||Journal Article, refereed|
|Communities & Collections:||04 Faculty of Medicine > Brain Research Institute|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||11 Feb 2008 12:13|
|Last Modified:||27 Nov 2013 16:35|
|Publisher:||National Academy of Sciences|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page