ROLE OF MNAV2.3 IN UTERINE CONTRACTION

描述 我们对足月子宫功能的了解仍然很差， 足月分娩中早产和子宫功能障碍是显著的 临床问题。越来越多的证据表明Na/+ 包括最近在Tamkun的克隆 实验室的一种新的电压门控钠通道（mNav2.3），这是向上- 在妊娠期间在子宫肌层中调节。广泛的长期目标 这项研究的目的是了解 Nav2.3通道在控制子宫收缩中的作用。 具体地，该提议首先寻求比较Na/+电流密度 小鼠子宫肌细胞中mNav2.3的表达 采用膜片钳技术和免疫组织化学方法检测妊娠期的子宫内膜。 第二，为了确定是否观察到的Na/+电流， 子宫肌细胞是由于表达Nav2.3基因，反义 设计用于抑制mNav2.3蛋白表达策略将用于 敲低Na/+通道电流。最后，使用 腺病毒载体递送编码天然Nav2.3通道的DNA 将对来自非妊娠小鼠的子宫肌细胞进行检测。实验 这项提案中概述的将决定Nav.23蛋白是否是 观察到的Na/+电流，并将有助于阐明其在 足月子宫收缩的调节。虽然早产是一个主要的 健康问题，因为它有出生缺陷的风险， 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， 解决这个问题。

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.