Comparison of Potassium Currents in Human Decidua Before and After the Onset of Labor1

Abstract

The human decidua plays a prominent role in the signaling between maternal and fetal tissues. It also secretes a plethora of molecules that modulate uterine function. Ion-channel activity underpins many cellular functions; however, the channels in human decidua have not been characterized in any detail. We have used the whole-cell recording mode of the patch-clamp technique to carry out current-clamp and voltage-clamp recordings of membrane properties and whole-cell potassium (K ؉ ) currents of freshly isolated decidual stromal cells. Decidual tissue was obtained from women after spontaneous vaginal delivery (SVD) or elective cesarean section (CS). Cells from both groups generated action potentials, the overshoots and durations of which were dependent on extracellular calcium levels, inhibited by cobalt and enhanced by barium. Potassium current (I K ) density was higher in the CS than in the SVD group. Outwardly directed currents were heterogeneous with respect to their activation/inactivation profiles and exhibited outward rectification. The main difference between the SVD and CS group was the presence of a sustained current component in CS cells that is tetraethylammonium chloride-resistant and appears to be unaffected by E-4031. No evidence for the activation of any calcium-activated K ؉ currents was obtained. We propose that human parturition is associated with subtle changes in K ؉ channel remodeling, reflecting the transition from uterine quiescence to activation and stimulation. An understanding of the signal transduction events underlying these process may eventually lead to novel approaches to prevent preterm labor via decidual rather than myometrial intervention.

SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of theKCNN3gene

“…One determinant of uterine quiescence is the activity of myometrial K ϩ channels (17,22). Generating both repolarizing and hyperpolarizing currents in MSMCs, these channels contribute significantly to uterine quiescence (7,21). Accordingly, their activities must be regulated as pregnancy progresses so that myometrial quiescence is maintained until labor.…”

Oxytocin Inhibits T-Type Calcium Current of Human Decidual Stromal Cells

“…Isolated decidual stromal cells were obtained by finely mincing the decidua into 1-2 mm 3 pieces, followed by incubation in 1 mg/ml collagenase in Ca 2ϩ /Mg 2ϩ -free Hanks' balanced salt solution at 37 C for 1 h. Thereafter, the cell preparation was layered onto 60% (v/v) Percoll and centrifuged at 800 ϫ g for 20 min, followed by two additional washes in PSS (100 ϫ g at 4 C) to yield a cell pellet. The latter was then incubated with CD45-coated Dynal beads to remove leukocytes as described previously (15). The purified decidual stromal cell preparation was immediately transferred into a second tube for electrophysiological studies after assessment of cell viability by trypan blue exclusion.…”

“…Our recent studies have demonstrated differential expression of voltage-dependent K ϩ currents with the onset of labor in decidual stromal cells (15), suggesting possible functional adaptations to delivery of the fetus. We describe here the modulation of T-type Ca 2ϩ current by OT in freshly dispersed stromal cells obtained before and after the onset of uncomplicated labor.…”

Macrophages Infiltrate the Human and Rat Decidua During Term and Preterm Labor: Evidence That Decidual Inflammation Precedes Labor1

“…However, little is known about inflammatory events in the decidua. The decidua is very immunologically active in early pregnancy [4,5] and, as the interface between maternal and fetal tissues, is ideally placed to coordinate inflammatory events via paracrine cross talk between the adjacent myometrium and fetal membranes [6]. Decidual activation, involving elevated prostaglandin and proinflammatory cytokine output, is proposed to be an early event in the labor process [7,8].…”