Plastic elimination of functional glutamate release sites by depolarization.
To examine persisting effects of depolarizing rises in extracellular potassium concentration ([K+](o)) on synapses, we depolarized cells to simulate ischemia-like rises in [K+](o). Elevated [K+](o) for 1-16 hr severely depressed glutamate signaling, while mildly depressing GABA transmission. The glutamate-specific changes were plastic over several hours and involved a decrease in the size of the pool of releasable vesicles. Rather than a reduction of the number of vesicles per release site, the change involved functional elimination of release sites. This change was clearly dissociable from a second effect, depressed probability of transmitter release, which was common to both glutamate and GABA transmission. Thus, while other recent evidence links alteration of the releasable pool size with changes in p(r), our results suggest the two can be independently manipulated. Selective depression of glutamate release may provide an adaptive mechanism by which neurons limit excitotoxicity.
Moulder
Krista L
KL
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Meeks
Julian P
JP
Shute
Amanda A
AA
Hamilton
Clair K
CK
de Erausquin
Gabriel
G
Mennerick
Steven
S
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018698:Glutamic Acid; D011189:Potassium Chloride; D002122:Calcium Chloride