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Gestation changes sodium pump isoform expression, leading to changes in ouabain sensitivity, contractility and intracellular calcium in rat uterus

Floyd, R.V., Mobasheri, Ali and Wray, S. (2017) Gestation changes sodium pump isoform expression, leading to changes in ouabain sensitivity, contractility and intracellular calcium in rat uterus Physiological Reports, 5.

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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  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 non-pregnant, 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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
Floyd, R.V.
Wray, S.
Date : 5 December 2017
DOI : 10.14814/phy2.13527
Copyright Disclaimer : © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords : Na+; K+-ATPase; Isoform;, Gestation; Myometrium; Smooth muscle; Immunohistochemistry
Depositing User : Clive Harris
Date Deposited : 10 Nov 2017 09:50
Last Modified : 16 Jan 2019 19:04

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