Multiple effects of spermine on N‐methyl‐D‐aspartic acid receptor responses of rat cultured hippocampal neurones.

作者：Morris Benveniste, Mark L. Mayer · 发表于：The Journal of Physiology · 年份：1993 · DOI：10.1113/jphysiol.1993.sp019627 · 被引用次数：201 · 研究领域：Polyamine Metabolism and Applications、Neuroscience and Neuropharmacology Research、Amino Acid Enzymes and Metabolism

1. The modulation by polyamines of responses to N-methyl-D-aspartic acid (NMDA) was studied using a rapid perfusion system and whole-cell voltage-clamp recording from rat hippocampal neurons in dissociated culture. 2. Concentration jump responses to 100 microM NMDA in the presence of 10 microM glycine revealed potentiation by 3 mM spermine at a membrane potential of +60 mV, but depression at -120 mV; the degree of potentiation at +60 mV was variable from cell to cell while marked depression at -120 mV was observed in all cells. The depression of responses to NMDA by spermine was highly voltage dependent (z delta = 1.17) with an apparent equilibrium dissociation constant for block at 0 mV of 27 mM. 3. Analysis of spermine dose-potentiation curves for responses recorded at +60 mV in the presence of 10 microM glycine revealed a half-maximal effect at 125 microM. Under the same conditions, but at -60 mV, analysis of spermine-evoked depression was performed for cells with less than 5% potentiation at +60 mV, and revealed half-maximal inhibition at 344 microM. 4. Dose-response analysis for the glycine-sensitive activation of NMDA receptors at +60 mV revealed a 3.5-fold increase in apparent affinity for glycine in the presence of 1 mM spermine. This increase in affinity for glycine was accompanied by a 3.3-fold decrease in the rate of development of glycine-sensitive desensitization, and a 2.4-fold decrease in the rate of dissociation of glycine from NMDA receptors, while the rate c...