Tribe R M, Moriarty P, Poston L
The London Myometrial Group, Fetal Health Research Group, Department of Obstetrics and Gynaecology, Guy's, King's and St. Thomas' School of Medicine, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
Biol Reprod. 2000 Sep;63(3):748-55. doi: 10.1095/biolreprod63.3.748.
A rise in intracellular calcium is the primary trigger for contractile activity in pregnant human myometrium. It is hypothesized that key proteins involved in myometrial calcium homeostasis are gestationally regulated and play an important role in the preparation for labor. The aims of the study were to investigate the role of sarcoplasmic reticulum Ca ATPases (SERCAs) in regulating spontaneous contractile activity in myometrium, and to determine the expression of SERCA isoforms 2a and 2b, and the plasma membrane Ca ATPase (PMCA), at term and during labor. Western blot analysis demonstrated that the expression of SERCA 2a and 2b significantly increased in myometrium of women in labor compared with those not in labor. The augmentation of contractile activity in laboring myometrium in the presence of a SERCA 2 inhibitor, cyclopiazonic acid (CPA), demonstrated the functional significance of this observation. It is interesting that the application of CPA in the presence of a calcium-activated potassium channel inhibitor to term nonlabor myometrium mimicked the response of myometrium from women in active labor to CPA alone. We conclude that the activity of SERCA isoforms becomes increasingly important in the maintenance of regular contractile activity during labor and may compensate for the functional loss of other calcium control pathways at term.
细胞内钙的升高是妊娠期间人子宫肌层收缩活动的主要触发因素。据推测，参与子宫肌层钙稳态的关键蛋白受孕期调节，并在分娩准备过程中发挥重要作用。本研究的目的是探讨肌浆网钙ATP酶（SERCAs）在调节子宫肌层自发收缩活动中的作用，并确定足月和分娩期间SERCAs亚型2a和2b以及质膜钙ATP酶（PMCA）的表达。蛋白质印迹分析表明，与未分娩的女性相比，分娩女性子宫肌层中SERCAs 2a和2b的表达显著增加。在存在SERCAs 2抑制剂环匹阿尼酸（CPA）的情况下，分娩子宫肌层收缩活动的增强证明了这一观察结果的功能意义。有趣的是，在存在钙激活钾通道抑制剂的情况下，将CPA应用于足月未分娩子宫肌层，其反应类似于活跃分娩女性子宫肌层对单独使用CPA的反应。我们得出结论，SERCAs亚型的活性在分娩期间维持规律收缩活动中变得越来越重要，并且可能在足月时补偿其他钙控制途径的功能丧失。
