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

Developmental and tissue‐specific differences in isoforms allow Na + , K + ‐ ATP ase function to be tightly regulated, as they control sensitivity to ions and inhibitors. Uterine contraction relies on the activity of the Na + , K + ATP ase, which creates ionic gradients that drive excitation‐contraction coupling. It is unknown whether Na + , K + ATP ase 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 + ATP ase α subunit inhibition with ouabain. Our aims were therefore: (1) to determine the gestation‐dependent expression of m RNA transcripts, protein abundance and tissue distribution of Na + , K + ATP ase 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 [Ca 2+ ]. Changes in abundance and distribution of the Na + , K + ATP ase α , β and FXYD 1 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 FXYD 1 were detected but FXYD 2 was absent. The α 1 and β 1 isoforms were unchanged throughout pregnancy, whereas α 2 and α 3 significant decreased at term while β 2 and FXYD 1 significantly increased from mid‐term onwards. These changes in expression correlated with increased functional sensitivity to ouabain, and parallel changes in intracellular Ca 2+ , measured with Indo‐1. In conclusion, gestation induces specific regulatory changes in expression of Na + , K + ATP ase isoforms in the uterus which influence contractility and may be related to the physiological requirements for successful pregnancy and delivery.