CALCIUM AND POTASSIUM CHANNELS IN LYMPHOCYTE

淋巴细胞中的离子通道具有多种功能， 包括抗原诱导的细胞内钙离子升高 与T细胞受体结合，淋巴因子分泌， 增殖 这些功能中的许多又被调节， 内源性和外源性物质，如儿茶酚胺， 类固醇，神经递质，尼古丁和滥用药物，以及 如疾病状态。 最近积累的大量证据表明， 提出了免疫调节物质或疾病 可以通过改变免疫原性来诱导或抑制特定的免疫功能。 淋巴细胞膜通道的特性。 这是主要目标， 这一建议阐明了细胞和分子机制， 哪些淋巴细胞通道启动、决定和调节免疫 反应 使用荧光和膜片钳记录技术， 将研究三种淋巴细胞离子的性质和调节 人类淋巴母细胞系中的通道，n型电压 依赖性钾通道K（V），钙依赖性钾通道 钾通道（Ca）和钙释放激活钙通道 （CRAC）。 这些通道的特性将在 某些类固醇激素、孕酮和雌二醇的影响， 新的海洋西松烷类化合物，其是衍生自 加勒比海软珊瑚（柳珊瑚）。 类固醇和毒素 检查它们对细胞内钙动员的影响， K（V）和K（Ca）的活化和失活动力学 通道，以及对Icrac（通过CRAC通道的电流）的影响。 获得的关于T淋巴细胞通道特性及其 调节将是非常有用的新的治疗设计 药物，主要针对这些膜离子通道。 工作 这里提出的将增加我们对T细胞调节的信息 通道及其免疫调节功能，并将有助于进一步 我们对免疫反应的理解以及如何控制它 在免疫缺陷，自身免疫， 炎症和其他疾病。

Ion channels in lymphocytes subserve a variety of functions, including the rise in intracellular calcium induced by antigen binding to the T cell receptor, and lymphokine secretion and proliferation. Manyof these functions are in turn modulated by endogenous and exogenous substances, such as catecholamines, steroids, neurotransmitters, and nicotine and drugs of abuse, as well as by disease states. Much recent evidence has accumulated to suggested the hypothesis that immunomodulating substances or diseases may induce or inhibit particular immune functions by altering the properties of lymphocyte membrance channels. It is the major goal of this proposal to elucidate the cellular and molecular mechanisms by which lymphocyte channels initate, determine and regulate the immune response. Using fluorescence and patch clamp recording techniques we will study the properties and regulation of three lymphocyte ion channels in a human lymphoblastoid cell line, the n type voltage dependent potassium channel K (V), the calcium dependent potassium channel K (Ca) and the calcium release-activated calcium channel (CRAC). The properties of these channels will be studied under the effects of certain steroid hormones, progesterone and estradiol, and novel marine cembranoids, which are diterpenoid toxins derived from Caribbean soft corals (gorgonians). The steroids and toxins will be examined for their effects on intracellular calcium mobilization and activation and inactivationkinetics in both the K (V) and K (Ca) channels, and for effects on Icrac (current through CRAC channels). The information obtained on T lymphocyte channel properties and their regulationwillb e very useful for the design of novel therapeutic agents, mainly targeted at these membrane ionic channels. The work proposed here will add to our information on the regulation of T cell channels and their immunomodulatory function, and will help further our understanding of the immune response and how to manage it successfully in states of immunodeficiency, autoimmunity, inflammation, and other disorders.