Roon R J, Koerner J F
Department of Biochemistry, Medical School, University of Minnesota, Minneapolis 55455, USA.
Brain Res. 1996 Sep 23;734(1-2):223-8.
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.
将大鼠海马体切片暴露于喹啉酸会使神经元对其他兴奋性氨基酸类似物（尤其是氨基酸膦酸盐）诱导的去极化作用的敏感性增强。膦酸盐可能作用于细胞外位点，因为通过用不含膦酸盐的孵育培养基冲洗，其去极化作用会迅速逆转。我们现在要报告一类新型的兴奋性氨基酸类似物，它们会诱导持续的去极化，且冲洗后不会逆转。将对喹啉酸敏感的大鼠海马体切片暴露于400微摩尔/升的L-天冬氨酸-β-异羟肟酸8分钟，会导致细胞外突触场电位完全抑制。在冲洗掉异羟肟酸化合物后，这种抑制至少持续1小时。类似的化合物L-谷氨酸-γ-异羟肟酸、D-天冬氨酸-β-异羟肟酸和膦酸盐衍生物L-2-氨基-3-膦酰丙酸（L-AP3）会诱导类似但较弱的场电位持续抑制。先前的研究还表明，将海马体切片暴露于L-α-氨基己二酸会阻断或逆转喹啉酸致敏作用，使神经元对膦酸盐化合物诱导的去极化无反应。我们现在报告，L-α-氨基己二酸也会阻断或逆转喹啉酸致敏神经元因暴露于异羟肟酸或L-AP3而诱导的持续去极化。
