Brines M L, Tabuteau H, Sundaresan S, Kim J, Spencer D D, de Lanerolle N
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Epilepsia. 1995 Apr;36(4):371-83. doi: 10.1111/j.1528-1157.1995.tb01012.x.
Na+,K(+)-ATPase (the sodium pump) is a ubiquitous enzyme that consumes ATP to maintain an adequate neuronal transmembrane electrical potential necessary for brain function and to dissipate ionic transients. Reductions in sodium pump function augment the sensitivity of neurons to glutamate, increasing excitability and neuronal damage in vitro. Temporal lobe epilepsy (TLE) is one disease characterized by hyperexcitability and marked hippocampal neuronal losses that could depend in part, on impaired sodium pump capacity secondary to changes in sodium pump levels and/or insufficient ATP supply. To assess whether abnormalities in the sodium pump occur in this disease, we used [3H]ouabain to determine the density of Na+,K(+)-ATPase for each anatomic region of hippocampus by in vitro autoradiography. Tissues were surgically obtained from epileptic patients with hippocampal sclerosis and compared with specimens from patients with seizures originating from temporal lobe tumors and autopsy controls. Changes in cellular population arising from neuronal losses or gliosis were assessed by protein densities derived from quantitative computerized densitometry of Coomassie-stained tissue sections. We estimated regional differences in capacity for ATP generation by determining cytochrome c oxidase (CO) activity. Principal neurons of hippocampus exhibit high levels of sodium pump enzyme. Both epilepsy groups exhibited slight but significant increases in sodium pump density/unit mass of protein in the dentate molecular layer, CA2, and subiculum as compared with autopsy controls. Greater hilar sodium pump density was also observed in sclerotic hippocampi. In contrast, CO activity was reduced in both epilepsy types throughout hippocampus. Results suggest that although sodium pump protein in surviving neurons appears to be upregulated in epilepsy, sodium pump capacity may be limited by the reduced levels of CO activity. Functional reduction in sodium pump capacity may be an important factor in hyperexcitability and neuronal death.
钠钾ATP酶（钠泵）是一种普遍存在的酶，它消耗ATP以维持大脑功能所需的适当神经元跨膜电势，并消散离子瞬变。钠泵功能的降低会增强神经元对谷氨酸的敏感性，增加体外兴奋性和神经元损伤。颞叶癫痫（TLE）是一种以兴奋性过高和明显的海马神经元丢失为特征的疾病，这可能部分取决于钠泵水平变化和/或ATP供应不足导致的钠泵功能受损。为了评估这种疾病中是否存在钠泵异常，我们使用[3H]哇巴因通过体外放射自显影法测定海马每个解剖区域的钠钾ATP酶密度。组织通过手术从患有海马硬化的癫痫患者身上获取，并与来自颞叶肿瘤引起癫痫发作的患者标本和尸检对照进行比较。通过考马斯亮蓝染色组织切片的定量计算机密度测定法得出的蛋白质密度来评估神经元丢失或胶质增生引起的细胞群体变化。我们通过测定细胞色素c氧化酶（CO）活性来估计ATP生成能力的区域差异。海马的主要神经元表现出高水平的钠泵酶。与尸检对照相比，两个癫痫组在齿状分子层、CA2和下托中钠泵密度/单位蛋白质质量均有轻微但显著的增加。在硬化的海马中也观察到更大的海马门钠泵密度。相比之下，两种癫痫类型的整个海马中的CO活性均降低。结果表明，尽管癫痫中存活神经元中的钠泵蛋白似乎上调，但钠泵能力可能受到CO活性降低水平的限制。钠泵能力的功能降低可能是兴奋性过高和神经元死亡的一个重要因素。
