Excitotoxicity, reflex responses, and evoked changes in extracellular potassium in the frog spinal cord

1. The effects of the excitatory amino acid agonists kainate (KA), quisqualate (QUIS), and N-methyl-D-aspartate (NMDA) were studied in vitro on the hemisected frog spinal cord. 2. Prolonged (1.0 hr) application of excitatory amino acid agonists (KA, 50 or 300 microM; QUIS, 30 microM; NMDA, 300 microM) significantly reduced the ventral root potentials (VRPs) and [K+]0 evoked by a dorsal root tetanus (10 sec, 25 Hz), by brief (10 sec) applications of the same agonists (KA, 30 microM; QUIS, 30 microM; NMDA, 300 microM), and by GABA (10 sec, 1.0 mM). 3. The effect was essentially irreversible and persisted despite 2-4 hr of washing. 4. Excitatory amino acid antagonists (APV, 30 microM and kynurenate, 2 mM) blocked the neurotoxic effects of the excitatory agonists NMDA and KA respectively, an observation which indicates the observed effects of the agonists require the activation of specific excitatory receptors. 5. TTX did not alter the neurotoxic effects of KA suggesting that interneuronal firing does not contribute to the observed changes. 6. Addition of high K+ did not duplicate the effect of prolonged excitatory amino acid agonist exposure, an indication that elevation of K+ does not cause the decreased responses. 7. Light microscopy did not provide any evidence of gross tissue damage. 8. The parallel reduction of postsynaptic responses and delta [K+]0 support the idea that elevation of extracellular [K+] by afferent stimuli results from interneuronal activity.