青蛙脊髓中的兴奋毒性、反射反应及细胞外钾离子的诱发变化。

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

Zhang D X, Hackman J C, Davidoff R A

Department of Neurology, University of Miami School of Medicine, FL.

Comp Biochem Physiol C Comp Pharmacol Toxicol. 1989;92(2):205-10. doi: 10.1016/0742-8413(89)90042-x.

Abstract

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.

摘要

在体外对半切的青蛙脊髓研究了兴奋性氨基酸激动剂红藻氨酸（KA）、quisqualate（QUIS）和N-甲基-D-天冬氨酸（NMDA）的作用。2. 长时间（1.0小时）应用兴奋性氨基酸激动剂（KA，50或300微摩尔；QUIS，30微摩尔；NMDA，300微摩尔），通过背根强直刺激（10秒，25赫兹）、短暂（10秒）应用相同激动剂（KA，30微摩尔；QUIS，30微摩尔；NMDA，300微摩尔）以及γ-氨基丁酸（10秒，1.0毫摩尔），显著降低了腹根电位（VRP）和由背根强直刺激诱发的[K⁺]₀。3. 这种作用基本上是不可逆的，即使经过2 - 4小时的冲洗仍持续存在。4. 兴奋性氨基酸拮抗剂（APV，30微摩尔和犬尿烯酸，2毫摩尔）分别阻断了兴奋性激动剂NMDA和KA的神经毒性作用，这一观察结果表明激动剂的观察到的作用需要特定兴奋性受体的激活。5. 河豚毒素（TTX）并未改变KA的神经毒性作用，表明中间神经元放电对观察到的变化没有贡献。6. 添加高钾并没有重现长时间暴露于兴奋性氨基酸激动剂的效果，这表明钾离子升高并不会导致反应降低。7. 光学显微镜未提供任何明显组织损伤的证据。8. 突触后反应和δ[K⁺]₀的平行降低支持了这样的观点，即传入刺激引起的细胞外[K⁺]升高是由中间神经元活动导致的。