CELLULAR CONTROL OF MEMBRANE CURRENTS

这个项目的长期目标是确定 细胞控制其细胞膜的离子电流。有两种方法 被使用：第一种方法侧重于膜的变化 环境中的更改可能导致的属性 薄膜。这些研究使用了蜗牛(Limnea， Helix，Helisoma)，在其上进行复杂的电生理研究 有可能。一种内灌流电压钳制技术已经被 开发出了允许细胞间以及 细胞外，离子和分子上的膜电流被测量。 将对细胞内钙电流的依赖性进行研究 正常情况下被灌流耗尽的分子，调节 通过外部施加神经递质产生的电压依赖电流， 膜性质与细胞功能的关系及其变化 体外维持对膜电流的影响以及生长的影响 温度对膜性能的影响。第二种方法检查 由点突变引起的细胞膜性质的变化 基因组。这些研究将在线虫的肌肉细胞上进行。 秀丽线虫，或果蝇的神经元胞体 果蝇；两种动物都便于进行遗传学研究。这个 内灌流电压钳技术已被证明适用于细胞 就像这些一样小。野生型动物的膜电流将是 确定了，然后来自一些行为突变的细胞将被 检查膜性能的变化。由于……的重要性 细胞内钙在控制肌肉收缩、递质释放、 和其他细胞功能，将在所有 上述研究对钙电流和重叠钾电流的影响， 这决定了钙进入细胞的情况。已发现的机制或 由该项目阐明的将大大有助于 对涉及状态改变的神经和肌肉疾病的理解 膜兴奋性或突触效能。

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.