LKS AND LKUR IN GRANULOSA CELLS

这项研究的长期目标是增加对离子的了解， 通道存在于卵巢颗粒细胞（GC），并提示可能 离子通道在GC功能中的作用。 拟议项目将侧重于 特别是对调控特性和功能意义的研究 缓慢激活、非失活延迟整流钾离子电流 (IKs)和超快速激活的延迟整流钾电流 （IKur）. 待检验的主要假设是：1）IKs和IKur是 受颗粒细胞信号转导系统的调节 生长和分化; 2）IKs、IKur或两者的钾电导 是正常颗粒细胞成熟所必需的。电生理 细胞培养技术将被用来解决这些假设 实验性的 生物化学技术将被用来定义 通道蛋白，有助于IKur。 具体来说，实验 1）比较颗粒细胞IKs的特性， 心脏慢延迟整流钾电流的那些，和 与min-K和KvLQT 1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和延迟的IKur的性质， 其他细胞类型的整流钾电流和延迟整流钾电流 与Kv（Shaker亚家族）通道表达相关的电流 蛋白质，有助于IKur; 3）确定是否有 不同钾通道拮抗剂对颗粒细胞抑制作用 成熟与IKs或IKur的阻断有关。 不仅要确定IKs的生理作用， 和IKur在GC成熟中的作用，而且还比较了 GC电流的曲线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、淋巴细胞和脑中（Carmeleit，1991）。 GC IKs和IKur可能代表辅助治疗的新靶点， 生殖，或潜在的毒性部位的药物设计，以治疗 心律失常、哮喘、失禁、免疫抑制或癫痫。

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.