Overexpression of SK3 Channels Dampens Uterine Contractility to Prevent Preterm Labor in Mice1
Open Access
- 1 June 2008
- journal article
- Published by Oxford University Press (OUP) in Biology of Reproduction
- Vol. 78 (6), 1058-1063
- https://doi.org/10.1095/biolreprod.107.066423
Abstract
The mechanisms that control the timing of labor have yet to be fully characterized. In a previous study, the overexpression of small conductance calcium-activated K+ channel isoform 3 in transgenic mice, Kcnn3tm1Jpad/Kcnn3tm1Jpad (also known as SK3T/T), led to compromised parturition, which indicates that KCNN3 (also known as SK3) plays an important role in the delivery process. Based on these findings, we hypothesized that SK3 channel expression must be downregulated late in pregnancy to enable the uterus to produce the forceful contractions required for parturition. Thus, we investigated the effects of SK3 channel expression on gestation and parturition, comparing SK3T/T mice to wild type (WT) mice. Here, we show in WT mice that SK3 transcript and protein are significantly reduced during pregnancy. We also found the force produced by uterine strips from Pregnancy Day 19 (P19) SK3T/T mice was significantly less than that measured in WT or SK3 knockout control (SK3DOX) uterine strips, and this effect was reversed by application of the SK3 channel inhibitor apamin. Moreover, two treatments that induce labor in mice failed to result in complete delivery in SK3T/T mice within 48 h after injection. Thus, stimuli that initiate parturition under normal circumstances are insufficient to coordinate the uterine contractions needed for the completion of delivery when SK3 channel activity is in excess. Our data indicate that SK3 channels must be downregulated for the gravid uterus to generate labor contractions sufficient for delivery in both term and preterm mice.Keywords
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