ROLE OF MNAV2.3 IN UTERINE CONTRACTION

MNAV2.3 在子宫收缩中的作用

• 批准号: 6138735
• 负责人: Jeffrey Martens
• 金额: $ 3.17万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6138735
• 关键词: antisense nucleic acid; birth; electrophysiology; female; gene expression; gestational age; laboratory mouse; muscle cells; muscle contraction; myometrium; pregnancy; sodium channel; sodium ion; uterus; voltage /patch clamp; voltage gated channel

DESCRIPTION Our understanding of uterine function at term remains poor while both preterm labor and uterine dysfunction in term labor are significant clinical problems. There is increasing evidence for a role of Na/+ channels in uterine contraction including the recent cloning in the Tamkun laboratory of a novel voltage gated sodium channel (mNav2.3) which is up- regulated in myometrium during pregnancy. The broad, long term objectives of this proposed research is to gain an understanding of the physiological role that the Nav2.3 channel plays in controlling uterine contraction. Specifically, this proposal seeks first to compare Na/+ current density and mNav2.3 expression in mouse uterine myocytes at different times in gestation using the patch clamp technique and immunohistochemical assays. Second, in order to determine to determine if the Na/+ current observed in uterine myocytes is due to expression of the Nav2.3 gene, antisense strategies design to inhibit expression of mNav2.3 protein will be used to knock-down Na/+ channel current. Finally, heterologous expression using adenoviral vectors to deliver DNA encoding the Nav2.3 channel in native uterine myocytes from non-pregnant mice will be performed. The experiments outlined in this proposal will determine if the Nav.23 protein underlies the observed Na/+ current and will help elucidate its role in the regulation of uterine contraction at term. While pre-term labor is a major health problem given the risk it carries with respect to birth defects and costs associated with premature delivery, a better understanding of the regulation of uterine contraction can only improve our ability to pharmacologically manage this problem.

描述 我们对足月子宫功能的了解仍然很差，而两者 早产和足月产时子宫功能障碍很重要 临床问题。越来越多的证据表明 Na/+ 的作用 子宫收缩通道，包括最近在 Tamkun 中的克隆 一种新型电压门控钠通道（mNav2.3）的实验室，它是上行的 怀孕期间在子宫肌层中受到调节。广泛、长期的目标 这项拟议研究的目的是为了了解生理学 Nav2.3 通道在控制子宫收缩中发挥的作用。 具体来说，该提案首先寻求比较 Na/+ 电流密度 不同时间小鼠子宫肌细胞中mNav2.3和mNav2.3的表达 使用膜片钳技术和免疫组织化学测定进行妊娠。 其次，为了确定是否观察到 Na/+ 电流 子宫肌细胞是由于 Nav2.3 基因的表达，反义 抑制 mNav2.3 蛋白表达的策略设计将用于 击倒Na/+通道电流。最后，使用异源表达 腺病毒载体可在天然环境中传递编码 Nav2.3 通道的 DNA 将使用来自非怀孕小鼠的子宫肌细胞。实验 该提案中概述的内容将确定 Nav.23 蛋白是否是 观察到的 Na/+ 电流将有助于阐明其在 足月子宫收缩的调节。虽然早产是一个主要的 考虑到其带来的出生缺陷风险和健康问题 与早产相关的费用，更好地了解 调节子宫收缩只能提高我们的能力 通过药物来解决这个问题。