Effects of kynurenate on root potentials evoked by synaptic activity and amino acids in the frog spinal cord

Abstract

The effects of kynurenate (kyn) on synaptic- and excitatory amino acid-mediated responses in isolated, hemisected spinal cords of frog were examined. Kyn (0.5 mM) rapidly and reversibly blocked >90% of the synaptically mediated ventral root potential (VRP) produced by stimulation of the dorsal root. Spontaneous activities recorded from both ventral and dorsal roots were also reversibly blocked by Kyn. However, Kyn had no effect on action potentials or excitability per se, nor was it a general inhinitor of synaptic transmission since Kyn concentrations as high as 2.5 mM had no effect on synaptically mediated dorsal root potentials produced by stimulation of the ventral root. In addition, Kyn had no effect on synaptic transmission in sympathetic ganglia of frog. Although Kyn (2.5 mM) by itself produced no ventral root response in spinal cords treated with tetrodotoxin, it antagonized those induced by the excitatory amino acids N-methyl- d,l-aspartate, quisqualite, kainate, aspartate, and glutamate. The ventral responsed to all concentrations of quisqualate tested were depressed by 2.5 mM Kyn. In addition, when Kyn was washed out, the rate of recovery from Kyn block was accelerated by the presence of quisqualate. These results indicate that quisqualate and Kyn compete for common binding sites. However, low concentrations of Kyn (e.g. 0.1 mM) potentiated the peak of the response to saturating concentrations of quisqualate by as much as 30%. The durations of the potentiated quisqualate responses were significantly shorter than the control responses. Thus, Kyn does not act simply as a competitive inhibitor of quisqualate. Incontrast, Kyn appears to simply block N-methyl- d,l-aspartate responses with no signs of poptentiation or charges in kinetics.