Taylor C P, Burke S P, Weber M L
Department of Neuroscience Pharmacology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
J Neurosci Methods. 1995 Jun;59(1):121-8. doi: 10.1016/0165-0270(94)00202-r.
We evaluated concentrations of excitatory amino acids released from slices into the superfusing solution and also evaluated extracellular field potential recordings and histological appearance of slice tissues to evaluate several sodium-channel modulating drugs as potential treatments for ischemia. The selective sodium-channel blocker tetrodotoxin (TTX, 1 microM) reduced glutamate release from deprivation of oxygen and D-glucose, while calcium-channel blockade was ineffective. Thus, during ischemia, we propose that glutamate may be released from the free cytosolic pool ('metabolic' glutamate) rather than by exocytosis. TTX (100-500 nM) and voltage-dependent sodium-channel blockers (phenytoin, 20-100 microM; lidocaine, 2-200 microM) each prevented damage to slices without blocking action potentials. The reduction of cellular depolarization and sodium loading during ischemia may explain the neuroprotective action of several sodium-channel modulating drugs in our in vitro studies and also in animal models.
我们评估了从脑片释放到灌流液中的兴奋性氨基酸浓度，还评估了细胞外场电位记录以及脑片组织的组织学外观，以评估几种钠通道调节药物作为缺血潜在治疗方法的效果。选择性钠通道阻滞剂河豚毒素（TTX，1微摩尔）可减少因缺氧和D - 葡萄糖剥夺导致的谷氨酸释放，而钙通道阻滞剂则无效。因此，在缺血期间，我们认为谷氨酸可能从游离胞质池（“代谢性”谷氨酸）释放，而非通过胞吐作用释放。TTX（100 - 500纳摩尔）和电压依赖性钠通道阻滞剂（苯妥英，20 - 100微摩尔；利多卡因，2 - 200微摩尔）均可防止脑片受损，且不阻断动作电位。缺血期间细胞去极化和钠负荷的降低可能解释了几种钠通道调节药物在我们的体外研究以及动物模型中的神经保护作用。
