CELLULAR CONTROL OF MEMBRANE CURRENTS

膜电流的细胞控制

• 批准号: 3074689
• 负责人: WILLIAM L. BYERLEY
• 金额: $ 5.32万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3074689
• 关键词: calcium metabolism; cell membrane; cytogenetics; genome; ion transport; membrane permeability; membrane potentials; muscle contraction; neurons; neurotransmitters; synapses

The long-term goal of this project is to determine the mechanisms by which cells control the ionic currents of their membranes. Two approaches are being used: the first approach focuses on the changes in membrane properties that can be induced by changes in the environment of the membrane. These studies use the neuronal cell bodies of snails (Limnea, Helix, Helisoma), on which sophisticated electrophysiological studies are possible. An internal-perfusion, voltage-clamp technique has been developed which allows the effects of interacellular, as well as extracellular, ions and molecules on membrane currents to be measured. Studies will be made of the dependence of Ca currents on intracellular molecules normally depleted by perfusion, the modulation of voltage-dependent currents by external application of neurotransmitters, the relation between membrane properties and cell function, the alteration of membrane currents by maintenance in vitro, and the effects of growth temperature on membrane properties. The second approach examines the changes in membrane properties that can be produced by point mutations in the genome. These studies will be done on the muscle cells of the nematode Caenorhabditis elegans, or neuronal cell bodies of the fruit fly Drosophila; both animals are convenient for genetic studies. The internal-perfusion, voltage-clamp technique has proven applicable to cells as small as these. The membrane currents of the wild-type animals will be determined, and then cells from a number of behavioral mutants will be examined for alterations in membrane properties. Due to the importance of interacellular Ca++ in controlling muscle contraction, transmitter release, and other cellular functions, primary attention will be given in all of the above studies to effects on the Ca current and overlapping K currents, which determine the influx of Ca++ into the cell. Mechanisms discovered or elucidated by this project will contribute significantly to the understanding of neural and muscular diseases that involve altered states of membrane excitability or synaptic efficacy.

该项目的长期目标是确定 细胞控制其膜的离子电流。 两种方法是 被使用：第一种方法着重于膜的变化 可以通过环境变化引起的属性 膜。 这些研究使用蜗牛的神经元细胞体（Limnea， Helix，Helisoma），复杂的电生理研究是 可能的。 内部灌注，电压钳技术已经 开发的，允许细胞间以及 细胞外，离子和分子待测量的膜电流。 将研究Ca电流对细胞内的依赖性 通常因灌注而耗尽的分子 通过外部应用神经递质，依赖电压的电流， 膜特性与细胞功能之间的关系，变化 通过体外维护和生长的影响 膜特性上的温度。 第二种方法检查了 可以通过点突变产生的膜特性的变化 基因组。 这些研究将在线虫的肌肉细胞上进行 秀丽隐杆线虫或果蝇的神经元细胞体 果蝇；两种动物都方便遗传研究。 这 内部灌注，电压钳技术已证明适用于细胞 这些小。 野生型动物的膜电流将是 确定，然后来自许多行为突变体的细胞将是 检查了膜特性的改变。 由于重要性 细胞间Ca ++在控制肌肉收缩，发射器释放中， 和其他细胞功能，将在所有中给出主要的关注 以上研究对CA电流和重叠K电流的影响， 确定Ca ++流入细胞的流入。 发现的机制或 该项目阐明将对 了解涉及改变状态的神经和肌肉疾病 膜兴奋性或突触功效。