Contributions of specific TrpCs to myometrial Ca2+ entry

特定 TrpC 对子宫肌层 Ca2 进入的贡献

• 批准号: 6985557
• 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
• 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/6985557
• 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

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）：了解怀孕期间调节肌层收缩的机制可能有助于避免诸如早产之类的情况。在分娩过程中，细胞内钙（Ca2+）的增加与人肌矩阵收缩密切相关。负责信号调节的Ca2+进入（SRCE）的潜在离子通道是瞬态受体电位（TRPC）通道的规范类型，假定会形成异性或同倍术，因此允许形成各种具有不同生理特性的通道。我们的主要目的是了解特定TRPC蛋白与Ca2+信号传导相关的功能作用，以阐明其在子宫肌层中的相对重要性。具体目的1）研究HTRPC4对人子宫骨骼中Ca2+动力学的贡献，2）确定HTRPD对人子宫骨骼中Ca2+动力学的功能，3）对确定HTRPC4 Plus HTRPC4 Plus HTRPD敲低的效果。通过使用基因沉默实验诱导特定TRPC蛋白的敲低研究，将研究具体目标。然后，将使用Fura-2荧光Ca2+指示器测量Ca2+水平来研究效果。