LKS AND LKUR IN GRANULOSA CELLS

颗粒细胞中的 LKS 和 LKUR

• 批准号: 6125589
• 负责人: Lisa C. Freeman
• 金额: $ 18.19万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6125589
• 关键词: animal tissue; cell differentiation; cell proliferation; cyclic AMP; electrophysiology; enzyme activity; female; granulosa cell; inhibitor /antagonist; potassium channel; protein kinase A; protein kinase C; reproductive system pharmacology; tissue /cell culture; voltage gated channel

The long-term goals of the research are to increase knowledge about ion channels present in ovarian granulosa cells (GC), and suggest potential roles for ion channels in GC function. The proposed project will focus specifically on the regulatory properties and functional significance of: a slowly activating, non-inactivating delayed rectifier K+ current (IKs), and an utra-rapidly activating delayed rectifier K+ curren (IKur). The major hypotheses to be tested are 1) IKs and IKur are modulated by signal transduction systems implicated in granulosa cell growth and differentiation; 2) IKs, IKur, or both potassium conductances are required for normal granulosa cell maturation. Electrophysiological and cell culture techniques will be used to address these hypotheses experimentally. Biochemical techniques will be used to define the channel proteins that contribute to IKur. Specifically, experiments were designed to: 1) Compare the properties of granulosa cell IKs to those of the cardiac slow delayed rectifier K+ current, and those of the slow K+ currents associated with co-expression of min-K and KvLQT1, the channel proteins that associate to form functional Ks channels; 2) Compare the properties of granulosa cell IKur to those of delayed rectifier K+ currents in other cell types, and delayed rectifier K+ currents associated with expression of the Kv (Shaker subfamily) channel proteins that contribute to IKur; 3) Determine whether or not the inhibitory effects of various K+ channel antagonists on granulosa cell maturation are related to blockade of IKs or IKur. It will be critical not only to define the physiological role(s) of IKs and IKur in GC maturation, but also to compare the pharmacological profiles of the GC currents to those of delayed rectifier currents in other cells. K+ channels have been identified as therapeutic targets in heart, smooth muscle, lymphocytes, and brain (Carmeleit, 1991). GC IKs and IKur may represent either novel targets for assisted reproduction, or potential sites of toxicity for drugs designed to treat arrhythmias, asthma, incontinence, immunosuppression or epilepsy.

该研究的长期目标是增加有关离子的知识 通道存在于卵巢颗粒细胞（GC）中，并表明潜在的 离子通道在 GC 功能中的作用。 拟议的项目将重点 特别是监管特性和功能意义 of：缓慢激活、非失活的延迟整流器 K+ 电流 (IKs)，以及超快速激活延迟整流器 K+ 电流 （伊库尔）。 要测试的主要假设是 1) IKs 和 IKur 是 由颗粒细胞中涉及的信号转导系统调节 生长和分化； 2) IKs、IKur 或两者钾电导 是正常颗粒细胞成熟所必需的。电生理学 细胞培养技术将用于解决这些假设 实验性地。 生化技术将用于定义 有助于 IKur 的通道蛋白。 具体来说，实验 旨在： 1) 比较颗粒细胞 IK 的特性 那些心脏慢延迟整流K+电流，和那些 与 min-K 和 KvLQT1 共表达相关的慢 K+ 电流， 结合形成功能性 Ks 通道的通道蛋白； 2） 比较颗粒细胞 IKur 与延迟细胞的特性 其他电池类型中的整流器 K+ 电流和延迟整流器 K+ 与 Kv（Shaker 亚家族）通道表达相关的电流 有助于 IKur 的蛋白质； 3）判断是否 各种K+通道拮抗剂对颗粒细胞的抑制作用 成熟与 IK 或 IKur 的封锁有关。 至关重要的不仅是定义 IK 的生理作用 和 IKur 在 GC 成熟中的作用，同时也比较了药理作用 GC电流与延迟整流器电流的曲线 其他细胞。 K+通道已被确定为治疗靶点 在心脏、平滑肌、淋巴细胞和大脑中（Carmeleit，1991）。 气相色谱 IKs 和 IKur 可能代表辅助的新目标 生殖，或设计用于治疗的药物的潜在毒性位点 心律失常、哮喘、失禁、免疫抑制或癫痫。