Persistent depression of synaptic responses occurs in quisqualate sensitized hippocampal slices after exposure to L-aspartate-beta-hydroxamate.
Exposure of slices of rat hippocampus to quisqualic acid produces an enhanced sensitivity of neurons to depolarization by other excitatory amino acid analogues, particularly amino acid phosphonates. The phosphonates may act at extracellular sites, since their depolarizing effects are rapidly reversed by washout with phosphonate-free incubation medium. We now wish to report a novel class of excitatory amino acid analogues that induce a persistent depolarization that is not reversed by washout. Exposure of quisqualate-sensitized slices of rat hippocampus to 400 microM L-aspartate-beta-hydroxamate for 8 min results in the complete depression of extracellular synaptic field potentials. This depression persists for at least 1 h after washout of the hydroxamate compound. Analogous compounds L-glutamate-gamma-hydroxamate, D-aspartate-beta-hydroxamate and the phosphonate derivative L-2-amino-3-phosphonopropanoic acid (L-AP3) induce a similar but weaker persistent depression of the field potentials. Previous studies also demonstrated that exposure of hippocampal slices to L-alpha-aminoadipate blocks or reverses quisqualate sensitization, making the neurons unresponsive to depolarization by phosphonate compounds. We now report that L-alpha-aminoadipate also blocks or reverses the persistent depolarization of quisqualate-sensitized neurons which is induced by exposure to the hydroxamates or L-AP3.
Department of Biochemistry, Medical School, University of Minnesota, Minneapolis 55455, USA.
R J
RJ
Roon
J F
JF
Koerner
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006877:Hydroxamic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D006877:Hydroxamic Acids; C000211:2-amino-3-phosphonopropionic acid; D015074:2-Aminoadipic Acid; C024848:beta-aspartylhydroxamic acid; D001216:Asparagine; D016318:Quisqualic Acid; D000409:Alanine