ROLE OF MNAV2.3 IN UTERINE CONTRACTION

MNAV2.3 在子宫收缩中的作用

• 批准号: 2767573
• 负责人: Jeffrey Martens
• 金额: $ 3.03万
• 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: 1999-06-08 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2767573
• 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 早产和足月分娩中的子宫功能障碍显著 临床问题。有越来越多的证据表明Na/+的作用 子宫收缩的途径，包括塔姆库恩的最新克隆 一种新型电压门控钠通道(mNav2.3)的实验室研究 在怀孕期间在子宫肌层中进行调节。宏大的长期目标 这项拟议的研究是为了了解生理学 Nav2.3通道在控制子宫收缩中的作用 具体地说，这项提议首先寻求比较Na/+电流密度 和mNav2.3在不同时间段小鼠子宫肌细胞中的表达 采用膜片钳技术和免疫组织化学方法。 其次，为了确定观察到的Na/+电流 子宫肌细胞表达Nav2.3基因，反义 将使用抑制mNav2.3蛋白表达的策略来 击倒Na/+通道电流。最后，异源表达使用 腺病毒载体在自然环境中传递编码Nav2.3通道的DNA 将对未怀孕小鼠的子宫肌细胞进行实验。这些实验 这份提案中概述的将决定Nav.23蛋白是否构成 观察到的Na/+电流，有助于阐明其在心肌细胞内的作用。 足月子宫收缩的调节。虽然早产是一个主要的 健康问题，因为它带有出生缺陷和 与早产相关的成本，更好地了解 调节子宫收缩只会提高我们的能力 从药物上解决这个问题。