THE PERMEABILITY OF AXON MEMBRANES

轴突膜的渗透性

• 批准号: 3395416
• 负责人: TED B BEGENISICH
• 金额: $ 10.95万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395416
• 关键词: Cephalopoda; antiarrhythmic agent; anticonvulsants; axon; barbiturates; brain disorder diagnosis; carboxyl group; carboxypeptidase; cell membrane; cesium; convulsants; drug adverse effect; drug receptors; electrophysiology; epilepsy; histidine; hydrogen bond; ion transport; lithium; local anesthetics; membrane permeability; membrane potentials; molecular biology; nervous system disorder chemotherapy; nervous system disorder diagnosis; neuroanatomy; neuronal transport; neuropharmacology; nonelectrolyte transport; p aminobenzoate; pentylenetetrazole; phenytoin; physical chemical interaction; potassium channel; rubidium; sodium channel; tetraethylammonium compound; tetrodotoxin; voltage /patch clamp; voltage gated channel

The membranes of excitable cells contain proteins that give these cells their special character. These protiens (called Na and K channels) are responsible for the time- and voltage-dependent permeability changes to Na and K ions that underlie the action potential and are also the receptors for local anesthetics and other neuroactive drugs. It is the long-term goal of this project to develop a molecular-level picture of these proteins using both electrophysiological and biochemical techniques on squid giant axons. Three immediate aims can be identified: 1) the use of protein modification techniques to investigate the importance of specific amino acids in the K channel gating and permeation processes. These processes are most readily studied with macroscopic currents obtained using axial-wire voltage clamp techniques on squid giant axons. Because of some limitations of macroscopic ionic current measurements, potassium channel gating currents and single channel currents will also be studied. 2) The involvement of carboxyl groups near the inner surface of sodium pores in the permeation process of Na channels will be studied. 3) The present picture of the sodium channel inactivation process will be re-examined. Specifically, experiments will be designed to determine if inactivation has an intrinsic voltage-dependence or derives its voltage-dependence from precursor steps in the gating process. Also, an attempt will be made to restore inactivation in axons whose inactivation has been removed by proteolytic enzymes. A knowledge of the important chemical groups of these proteins and a detailed knowledge of the interactions of drugs with the proteins will ultimately be useful in understanding the properties of the porteins in pathological conditions and in designing new therapeutic agents wih fewer side effects.

可兴奋细胞的膜含有蛋白质，使这些细胞 他们的特殊性格。 这些蛋白质（称为 Na 和 K 通道）是 负责 Na 随时间和电压变化的磁导率变化 和 K 离子是动作电位的基础，也是受体 用于局部麻醉剂和其他神经活性药物。 这是长期的 该项目的目标是开发这些蛋白质的分子水平图像 在巨型鱿鱼身上使用电生理学和生化技术 轴突。 可以确定三个近期目标：1）蛋白质的使用 修饰技术来研究特定氨基的重要性 K 通道门控和渗透过程中的酸。 这些过程 最容易研究使用获得的宏观电流 鱿鱼巨轴突上的轴向线电压钳技术。 因为一些 宏观离子电流测量的局限性，钾通道 还将研究门控电流和单通道电流。 2) 的 钠孔内表面附近的羧基参与 研究Na通道的渗透过程。 3）现在 钠通道失活过程的图片将被重新检查。 具体来说，将设计实验来确定失活是否已发生 固有的电压依赖性或从其导出其电压依赖性 门控过程中的前驱步骤。 此外，还将尝试 恢复失活已被去除的轴突的失活 蛋白水解酶。 了解这些蛋白质的重要​​化学基团和 药物与蛋白质相互作用的详细知识将 最终有助于理解蛋白质的特性 病理条件和设计新的治疗药物更少 副作用。