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

Susan Wray,Ali Mobasheri,Rachel V Floyd

doi:10.14814/phy2.13527

Susan Wray, Ali Mobasheri + Show 1 more

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https://doi.org/10.14814/phy2.13527

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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 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.

Highlights

The excitability of human myometrium must be regulated to control contractile activity for successful pregnancy and parturition (Wray et al 2003, 2015; Noble et al 2009)
The expression of multiple isoforms of the Na+, K+ ATPase and FXYD1 and FXYD2 was studied in nonpregnant rat uterus and at different stages of pregnancy
It is appreciated that the Na+, K+ ATPase activity is modified by the expression of different isoforms of its molecular subunits, and so a determination of their expression and isozyme combination in the myometrium will increase our understanding of how the Na+, K+ ATPase will contribute to excitation-contraction coupling during different stages of pregnancy

Summary

Introduction

The excitability of human myometrium must be regulated to control contractile activity for successful pregnancy and parturition (Wray et al 2003, 2015; Noble et al 2009). Either directly (Na+, K+) or indirectly (Ca2+, ClÀ), the concentrations of these ions are dependent upon the Na+, K+-ATPase, as it moves 3Na+ out of the cell with 2K+ entering and contributes to the negative cell membrane potential and the differential concentration gradients of sodium and potassium. The ion distributions across the cell membrane can be linked to the entry or efflux of other ions, including Ca2+, ClÀ and protons, all of which will affect myometrial excitability (Wray et al 2015). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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