Gestation changes sodium pump isoform expression, leading to changes in ouabain sensitivity, contractility, and intracellular calcium in rat uterus.
Gestation changes sodium pump isoform expression, leading to changes in ouabain sensitivity, contractility, and intracellular calcium in rat uterus.
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DOI：
10.14814/phy2.13527
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发表时间：
2017-12
影响因子：
2.5
通讯作者：
Wray S
中科院分区：
文献类型：
--
作者：
Floyd RV;Mobasheri A;Wray S
发育和组织特异性亚型的差异允许Na+，K+-ATPase功能受到严格调控，因为它们控制着对离子和抑制剂的敏感性。子宫收缩依赖于Na+，K+ATPase的活性，该酶产生离子梯度，驱动兴奋-收缩耦合。目前尚不清楚Na+，K+ATPase亚型是否在整个妊娠过程中受到调节，或者它们是否在调节子宫收缩中起到直接作用。我们推测，与妊娠相关的异构体差异表达将影响哇巴因抑制Na+，K+-ATPaseα亚单位的收缩反应。因此，我们的目标是：(1)确定子宫肌层中Na+，K+ATPase亚型与妊娠相关的mRNA表达、蛋白丰度和组织分布；(2)通过哇巴因敏感性来研究不同亚型表达的功能效应；(3)收缩反应的变化是否可以用细胞内[Ca~(2+)]的变化来解释。研究了大鼠子宫Na+，K+ATPaseα，β和FXYD12个亚型在未孕、早、中、足月妊娠大鼠子宫中丰度和分布的变化。α，β亚基亚基(1，2，3)和FXYD1均可检测到，但FXYD2缺失。α-1和β-1亚型在整个妊娠期间没有变化，而α-2和α-3在足月时显著降低，而β-2和FXYD_1在中期以后显著升高。这些表达的变化与哇巴因功能敏感性的增加以及INDO-1测量的细胞内钙的平行变化有关。总之，妊娠诱导子宫中Na+，K+ATPase亚型表达的特定调节变化，影响收缩，并可能与成功妊娠和分娩的生理要求有关。
Developmental and tissue‐specific differences in isoforms allow Na+, K+‐ATPase function to be tightly regulated, as they control sensitivity to ions and inhibitors. Uterine contraction relies on the activity of the Na+, K+ ATPase, which creates ionic gradients that drive excitation‐contraction coupling. It is unknown whether Na+, K+ ATPase isoforms are regulated throughout pregnancy or whether they have a direct role in modulating uterine contractility. We hypothesized that gestation‐dependent differential expression of isoforms would affect contractile responses to Na+, K+ ATPase α subunit inhibition with ouabain. Our aims were therefore: (1) to determine the gestation‐dependent expression of mRNA transcripts, protein abundance and tissue distribution of Na+, K+ ATPase isoforms in myometrium; (2) to investigate the functional effects of differential isoform expression via ouabain sensitivity; and (3) if changes in contractile responses can be explained by changes in intracellular [Ca2+]. Changes in abundance and distribution of the Na+, K+ ATPase α, β and FXYD1 and 2 isoforms, were studied in rat uterus from nonpregnant, and early, mid‐, and term gestation. All α, β subunit isoforms (1,2,3) and FXYD1 were detected but FXYD2 was absent. The α1 and β1 isoforms were unchanged throughout pregnancy, whereas α2 and α3 significant decreased at term while β2 and FXYD1 significantly increased from mid‐term onwards. These changes in expression correlated with increased functional sensitivity to ouabain, and parallel changes in intracellular Ca2+, measured with Indo‐1. In conclusion, gestation induces specific regulatory changes in expression of Na+, K+ ATPase isoforms in the uterus which influence contractility and may be related to the physiological requirements for successful pregnancy and delivery.