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，其发生的规律性和强度非常显著。子宫肌层(子宫肌肉)收缩会引起宫内压力的周期性增加，这是充分分娩的临床特征。随着压力的增加，宫颈扩张，婴儿出生。子宫异常收缩(早产或过弱)可导致严重的、有时危及生命的并发症(如早产、功能障碍、产后宫缩乏力等)。因此，重要的是要弄清子宫收缩的开始和时间的机制。子宫收缩是由细胞质中钙离子浓度的增加触发的，而当细胞质钙水平下降时，则发生松弛。细胞质钙的升高是由细胞膜上的一种称为动作电位的电刺激事件触发的。这项建议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，我们认为Kir7.1在减少兴奋方面非常重要，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通常会减少，子宫的兴奋性增加，以允许分娩所需的收缩。在这项提案中，我们将详细描述Kir7.1蛋白的行为，并调查其功能过早丧失是否会导致婴儿早产。我们还将调查分娩时Kir7.1的过多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，这可能会导致针对这些毁灭性疾病的新疗法。我们还应该增加对劳动过程本身的了解。

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.