Date of Degree
PhD (Doctor of Philosophy)
Molecular Physiology and Biophysics
Sarah K. England
SK3 channels contribute to membrane repolarization and hyperpolarization that leads to both relaxation of smooth muscle and vascular branching. These two distinct properties are intensified in the SK3T/T mice possibly influencing pregnancy by dampening uterine contractions and causing dysfunctional placental development. SK3T/T mice have delayed or hindered parturition, suggesting a role for SK3 channels in labor contractions (Chapter 2 & 3). Based on these findings, we hypothesized that SK3 channel expression must be reduced late in normal pregnancy to enable the uterus to produce the forceful contractions required for parturition. The mechanism(s) downregulating this channel in the uterus during pregnancy is unknown. The SK3 gene promoter region contains two Specificity Protein (Sp) binding sites; Sp1, a transcription factor that enhances transcription of genes in response to estrogen, and Sp3, a factor that competes for the same binding motif as Sp1 to reduce gene expression (Chapter 4). SK3 channels may also be involved in the vascular remodeling that occurs during pregnancy. The SK3 channel is present in vascular endothelial cells and overexpression of this channel leads to abnormal vessel branching and an increase in vessel diameter. During pregnancy, the vascular system must adapt to accommodate dramatic increases in blood volume necessary to sustain the developing fetus. Overexpression of SK3 channels could produce abnormalities in the placental vascular network, similar to the abnormal vessel branching and vasodilatation found in the mesenteric circulation, thus leading to poor fetal outcome (Chapter 5). The aim of this research was to determine the function of the SK3 channel in pregnancy by focusing on its role in myometrial contractility in addition to identifying its role in remodeling the maternal vasculature and its impact on placental blood flow and fetal demise.
mouse model, parturition, placenta, pregnancy, SK3 channels, uterus
xiv, 143 pages
Includes bibliographical references (pages 131-143).
Copyright 2010 Stephanie Lynn Pierce