EFECTS OF DEMYELINATION AND AGING UPON SODIUM CHANNELS

钠通道是一种跨膜蛋白，它调节电压。 电可激发膜的钠渗透性。它的 存在对于生物的产生和传播具有明显的重要性 沿轴膜的动作电位。使用具有良好特性的抗体 针对钠通道和免疫细胞化学/放射免疫分析 方法，我们计划分别研究实验性脱髓鞘和 衰老影响神经组织中的钠通道。 在第一组观察中，我们将测定和对比钠 周围神经轴突脱髓鞘的经络分布和数量 急性使用亚碲酸钾，亚急性使用衣霉素，以及 长期服用阿霉素。这些研究应该有助于我们理解 脱髓鞘的轴突被重塑以重新建立传导。是这样的 自从轴突传导恢复以来，信息很重要 是许多人类脱髓鞘疾病康复的基础。 在第二组观察中，我们将确定钠通道 老年神经组织的分布和数量及其与 它们在幼年神经组织中的分布和数量。一个老牌的 和经过充分研究的老龄大鼠群体将提供充足的老龄大脑和 外周神经为本研究的一部分。在另一系列单独的 观察我们将检查受影响的人脑组织中的钠通道 由与衰老相关的疾病引起的。一个特殊的利益将是 对阿尔茨海默病患者的尸检。这些 研究应该揭示衰老本身或与之相关的疾病 衰老导致可生化检测到的钠离子通道的变化 可能最终导致神经元功能障碍。这样的信息很重要 由于人们对衰老或疾病的机制知之甚少 神经元失去了功能的能力。

The sodium channel is a transmembrane protein that mediates the voltage dependent sodium permeability of electrically excitable membranes. Its presence is of obvious importance for the generation and propagation of action potentials along axolemma. Using well characterized antibodies directed against sodium channels and immunocytochemical/radioimmunoassay methods, we plan to study separately how experimental demyelination and aging affect sodium channels in nervous tissues. In the first set of observations we will determine and contrast sodium channel distribution and quantity along peripheral nerve axons demyelinated acutely with potassium tellurite, subacutely with tunicamycin, and chronically with doxorubicin. These studies should help us understand how demyelinated axons become remodelled to re-establish conduction. Such information is important since the resumption of axonal conduction appears to be the basis for recovery in many human demyelinating diseases. In the second set of observations we will determine sodium channel distribution and quantity in aged nervous tissue and contrast this with their distribution and quantity in young nervous tissue. An established and well studied aging rat colony will provide ample aged brain and peripheral nerve for one part of this study. In a separate series of observations we will examine sodium channels in human brain tissue affected by diseases associated with aging. A special interest will be the examination of postmortem brain afflicted with Alzheimer's disease. These studies should reveal whether aging per se or diseases associated with aging result in biochemically detectable changes in sodium channels that could culminate in neuronal dysfunction. Such information is important since little is known regarding the mechanisms by which aging or diseased neurons lose their ability to function.