Acute decrease in net glutamate uptake during energy deprivation

Denis Jabaudon

doi:10.1073/pnas.97.10.5610

2000-05-09

238

DOI：10.1073/pnas.97.10.5610

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摘要

En 中文

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 approximate to 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.

Keyword:

RAT HIPPOCAMPAL-NEURONS

D-ASPARTATE RECEPTORS

IN-VITRO ISCHEMIA

NMDA RECEPTORS

SYNAPTIC TRANSMISSION

UPTAKE INHIBITION

XENOPUS-OOCYTES

TETANUS TOXIN

GLIAL-CELLS

RELEASE