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

Floyd, Rachel V, Mobasheri, Ali and Wray, Susan ORCID: 0000-0002-0086-1359 (2017) Gestation changes sodium pump isoform expression, leading to changes in ouabain sensitivity, contractility, and intracellular calcium in rat uterus. PHYSIOLOGICAL REPORTS, 5 (23). e13527-.

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Abstract

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 <i>α</i> 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 <i>α</i>, <i>β</i> and FXYD1 and 2 isoforms, were studied in rat uterus from nonpregnant, and early, mid-, and term gestation. All <i>α</i>, <i>β</i> subunit isoforms (1,2,3) and FXYD1 were detected but FXYD2 was absent. The <i>α</i>1 and <i>β</i>1 isoforms were unchanged throughout pregnancy, whereas <i>α</i>2 and <i>α</i>3 significant decreased at term while <i>β</i>2 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
Uncontrolled Keywords:	Gestation, immunohistochemistry, isoform, K+-ATPase, myometrium, Na+, smooth muscle
Depositing User:	Symplectic Admin
Date Deposited:	08 Dec 2017 13:45
Last Modified:	15 Mar 2024 01:34
DOI:	10.14814/phy2.13527
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3013772