THE PERMEABILITY OF AXON MEMBRANES

轴突膜的渗透性

• 批准号: 3395411
• 负责人: TED B BEGENISICH
• 金额: $ 10.18万
• 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 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395411
• 关键词: antiarrhythmic agent; anticonvulsants; axon; barbiturates; brain disorder diagnosis; carboxyl group; carboxypeptidase; cell membrane; cesium; convulsants; drug adverse effect; 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; rubidium; tetraethylammonium compound; tetrodotoxin

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.

可激发细胞的膜含有蛋白质，可为这些细胞提供这些细胞 他们的特殊角色。 这些protien（称为Na和K通道）是 负责时间和电压依赖性的渗透性变化Na 和基于动作潜力的基础，也是受体 用于局部麻醉药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级图片 在鱿鱼巨型上使用电生理和生化技术 轴突。 可以确定三个直接目标：1）使用蛋白质 修改技术以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 最容易用使用宏观电流来研究 鱿鱼巨型轴突上的轴线电压夹具技术。 因为有些 宏观离子电流测量，钾通道的局限性 还将研究门控电流和单个通道电流。 2） 钠孔内表面附近的羧基参与 将研究NA通道的渗透过程。 3）现在 将重新检查钠通道失活过程的图片。 具体而言，将设计实验以确定失活是否具有 固有电压依赖性或从中依赖性电压依赖性 门控过程中的前体步骤。 另外，将尝试 轴突中的失活的恢复，其失活已被消除 蛋白水解酶。 了解这些蛋白质的重要​​化学基团和A 详细了解药物与蛋白质相互作用的知识将 最终有助于理解porteins在 病理状况和设计新的治疗剂， 副作用。