The role of the inwardly rectifying potassium channel Kir 7.1 in maintenance of uterine quiescence during pregnancy.

分娩中的妇女经历子宫收缩，其发生具有显著的规律性和力量。子宫肌层（子宫的肌肉）收缩产生子宫内压的周期性增加，这是充分分娩的临床标志。随着压力的增加，子宫颈扩张，婴儿出生。子宫收缩异常（过早或过弱）可导致严重的，有时甚至危及生命的并发症（例如早产、功能障碍性分娩、产后子宫收缩乏力等）。因此，重要的是要解开的机制，负责子宫收缩的启动和时间。子宫的收缩是由细胞质中钙离子浓度的增加触发的，而松弛发生在细胞质钙水平降低时。细胞质钙离子的升高是由细胞膜上的电激发事件触发的，称为动作电位。该提案研究了一种影响子宫肌细胞电兴奋过程的蛋白质（Kir 7.1）。在怀孕期间，我们提出Kir7.1在减少兴奋方面很重要，因此在婴儿发育期间阻止子宫收缩。随着分娩时间的临近，Kir7.1通常会降低，子宫的兴奋性增加，以允许分娩婴儿所需的收缩。在这项提案中，我们将详细介绍Kir7.1蛋白的作用，并研究其功能的过早丧失是否会导致婴儿早产。我们还将研究分娩时Kir7.1的过度活动是否会导致分娩期间子宫收缩不良。在研究过程中，我们将研究一种旨在抑制Kir7.1的新药，这可能会为这些毁灭性的疾病带来新的治疗方法。我们还应该增加对劳动过程本身的认识。

Women in labour experience uterine contractions that occur with remarkable regularity and force. Myometrial (muscle of the womb) contractions generate periodic increases in intrauterine pressure, which is the clinical hallmark of adequate labour. With pressure increases, the cervix dilates and the baby is delivered. Abnormal (premature or too weak) contractions of the uterus can lead to serious and sometimes life threatening complications (e.g. preterm labour, dysfunctional labour, post partum uterine atony, etc). It is therefore important to unravel the mechanisms responsible for the initiation and timing of uterine contractions. The contraction of the uterus is triggered by an increase in the concentration of calcium ions in the cytoplasm of the cell, while relaxation occurs when cytoplasmic calcium level decreases. The rises in cytoplasmic calcium are triggered by an electrical excitation event at the cellular membrane called an action potential. This proposal investigates a protein (Kir 7.1) that affects the process of electrical excitation in uterine muscle cells. During gestation we propose Kir7.1 is important in reducing excitation and therefore stopping the uterus from contracting whilst the baby in developing. As the time for delivery approaches Kir7.1 would normally decrease and the excitability of the uterus increase to allow the contractions needed to deliver the baby. During this proposal we will characterise in detail the actions of the protein Kir7.1 and investigate whether premature loss of its function leads to babies being born prematurely. We will also investigate whether too much activity of Kir7.1 at the time of labour leads to poor contractions of the uterus during delivery. During the course of the study we will investigate a novel drug aimed at inhibiting Kir7.1 which may lead to new treatments for these devastating conditions. We should also increase our knowledge of the labour process itself.