%0 Journal Article
%T The Small-Conductance Ca2+-Activated Potassium Channel, Subtype SK3, in the Human Myometrium Is Downregulated in Early Stages of Pregnancy
%A M. Rahbek
%A S. T. Rosenbaum
%A M. J. Dahl
%A D. A. Klaerke
%A L. £¿dum
%A S. S. Poulsen
%A T. Larsen
%A P. Bouchelouche
%J Physiology Journal
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/584717
%X The human myometrium is mainly relaxed during pregnancy, but, up to term, contractions become more coordinated and forceful in order to initiate delivery. Small conductance Ca2+-activated K+ channels (SK channels) in human myometrium have been shown to be downregulated in late pregnancy. The aim was to investigate the presence of SK2 and SK3 in the human myometrium from nonpregnant women, pregnant women at term, and pregnancies delivered preterm and, in addition, to characterize the time of downregulation of these channels. Using qRT-PCR, we observed significantly lower levels of mRNA for SK2 than for SK3 in the nonpregnant tissue. The mRNA levels of SK3 were significantly reduced in tissue from pregnancies at term and pregnancies resulting in preterm deliveries, whereas no downregulation for SK2 was observed. Western blotting confirmed the qRT-PCR results. Using immunohistochemical staining, both SK2 and SK3 were detected in endometrial glandular epithelium. We conclude that SK3 mRNA is downregulated early in pregnancy¡ªat least among those that result in preterm deliveries. Furthermore, we find that SK channels are expressed not only in the uterine smooth muscle but also in the endometrial epithelium. 1. Introduction Preterm births (delivery before 37 weeks of gestation) account for 9.6% of all births worldwide [1], and the number appears to be rising [2]. Death of the infant due to a preterm birth accounts for 28% of all neonatal deaths globally [3] which makes the issue of a great importance. Treatment available at present is able to delay birth only by approximately 1-2 days, which most often is insufficient to avoid severe complications for the newborn. Thus, there is a need for new and more efficient methods for treatment, calling for improved knowledge regarding the factors contributing to premature delivery. Recently, focus has been on the K+ channels and their contribution to the quiescence of the myometrium during pregnancy. Through their role in hyperpolarization, the channels are able to modulate excitability and contractility of the muscle cell. Several potassium channels including KCNQ channels [4], ATP-sensitive potassium channels [5], stretch-activated two-pore potassium channels [6], and big conductance Ca2+-activated potassium channels [7, 8] have been identified in human myometrium, and most of these channels are downregulated during late pregnancy. The small conductance Ca2+-activated potassium channel (SK channels) comprise three members (SK1-3) [9]. SK3 has been described in mouse myometrium of genetically altered mice, where an
%U http://www.hindawi.com/journals/physiology/2013/584717/