Contributions of specific TrpCs to myometrial Ca2+ entry

特定 TrpC 对子宫肌层 Ca2 进入的贡献

基本信息

批准号：
7110350
负责人：
Aida E Ulloa
金额：
$ 2.65万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-15 至 2008-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7110350
关键词：
calcium channel calcium flux calcium indicator calcium ion calcium metabolism disease /disorder prevention /control gene expression gene induction /repression human tissue intracellular transport ion transport muscle contraction myometrium predoctoral investigator pregnancy premature labor protein structure function tissue /cell culture

项目摘要

DESCRIPTION (provided by applicant): Understanding the mechanisms regulating contractions in the myometrium during pregnancy may help avoid scenarios such as premature births. During labor, increases in intracellular calcium (Ca2+) are closely correlated with human myometrium contractions. Potential ion channels responsible for Signal-Regulated Ca2+ Entry (SRCE) are the canonical type of transient receptor potential (TrpC) channels, postulated to form hetero- or homotetramers thus, allowing formation of a variety of channels possessing different physiological properties. Our main objective is to understand the functional roles of specific TrpC proteins in relation to Ca2+ signaling to elucidate their relative significance in myometrium. Specific aims 1) To study the contribution of hTrpC4 to Ca2+ dynamics in human myometrium, 2) To determine the function of hTrpd on Ca2+ dynamics in human myometrium, 3) To determining the effect of hTrpC4 plus hTrpd knockdown in human myometrium. Specific aims will be studied by the use of gene silencing experiments to induce knockdown of the specific TrpC proteins. Effects will then be studied by measuring Ca2+ levels using Fura-2 fluorescent Ca2+ indicator.

描述（由申请人提供）：了解怀孕期间调节子宫肌层收缩的机制可能有助于避免早产等情况。在分娩过程中，细胞内钙（Ca2+）的增加与人类子宫肌层的收缩密切相关。负责信号调节 Ca2+ 进入 (SRCE) 的电位离子通道是瞬时受体电位 (TrpC) 通道的典型类型，假定形成异四聚体或同四聚体，从而允许形成具有不同生理特性的多种通道。我们的主要目标是了解特定 TrpC 蛋白与 Ca2+ 信号传导相关的功能作用，以阐明它们在子宫肌层中的相对重要性。具体目标 1) 研究 hTrpC4 对人类子宫肌层 Ca2+ 动态的贡献，2) 确定 hTrpd 对人类子宫肌层 Ca2+ 动态的功能，3) 确定 hTrpC4 加 hTrpd 敲低对人类子宫肌层的影响。将通过使用基因沉默实验来诱导特定 TrpC 蛋白的敲低来研究特定目标。然后使用 Fura-2 荧光 Ca2+ 指示剂测量 Ca2+ 水平来研究效果。