REGULATION OF HEART CELL FUNCTION BY MEMBRANE COMPONENTS

每个细胞都被质膜包围，质膜将细胞质与细胞质分开 细胞外液并将一个细胞与另一个细胞分开。 膜和 膜相关成分几乎在各个方面都发挥着至关重要的作用 的细胞功能。 在胚胎发育过程中， 各种组织型细胞特性与基因相关 表面相关分子（例如受体）的受控改变 用于激素和神经递质、转运蛋白和离子电导 渠道。 本计划的目标是了解如何确定 细胞膜的特定成分和膜相关的 细胞骨架作为细胞功能的调节者，以及这些变化如何发生 组件的开发导致最终的实现 可兴奋细胞的功能状态。 通过应用生化法， 生物物理、遗传和超微结构技术对心肌细胞的影响 大量的体外模型系统，我们希望深入了解 膜功能的机制。 该计划的统一主题 是细胞表面成分在调节细胞功能中的作用。 那里 是三种主要方法。 其中一项工作重点是特定离子电导 心脏细胞膜的机制；它们在胚胎中如何发育 心脏，以及它们在宏观和微观电学中的作用 活动。 第二个焦点涉及胰岛素的受体机制和 乙酰胆碱，以及这些配体如何激活电流和其他细胞 活动。 第三个领域是生理和遗传调控。 细胞膜中的离子传输机制。 这是一个更新提案 感谢七名经验丰富的人五年来对扩大努力的支持 调查人员。 该计划包括七个相互关联的项目 由六大核心设施组成。

Every cell is surrounded by a plasma membrane that divides cytoplasm from extracellular fluid and separates one cell from another. The membrane and membrane-associated components play vital roles in virtually every aspect of cell function. During embryonic development, the differentiation of a variety of histotypic cell properties is associated with gentically controlled alterations in surface-associated molecules such as receptors for hormones and neurotransmitters, transport proteins and ion conductance channels. It is the goal of this Program to understand how certain specific components of the cell membrane and the membrane-associated cytoskeleton serve as regulators of cell function, and how changes in these components with development result in the achievement of definitive functional states in excitable cells. By application of biochemical, biophysical, genetic, and ultrastructural techniques to cardiac cells in a number of in vitro model system, we hope to gain insight into the mechanisms underlying membrane function. The unifying theme of the Program is the role of cell surface components in regulating cell function. There are three major approaches. One effort focuses on specific ion conductance mechanisms in the heart cell membrane; how they develop in the embryonic heart, and what role they have in macroscopic and microscopic electrical activity. A second focus deals with receptor mechanisms for insulin and acetylcholine, and how these ligands activate currents and other cellular activities. The third area is the physiological and genetic regulation of ion transport mechanisms in the cell membrane. This is a renewal proposal for five years of support for an expanded effort by seven experienced investigators. The Program includes seven inter-related projects subserved by six core facilities.