Journal article
Overexpression of SK3 Channels Dampens Uterine Contractility to Prevent Preterm Labor in Mice
Biology of reproduction, Vol.78(6), pp.1058-1063
06/2008
DOI: 10.1095/biolreprod.107.066423
PMCID: PMC2930016
PMID: 18305226
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,
Kcnn3
tm1Jpad
/
Kcnn3
tm1Jpad
(also known as SK3
T/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 SK3
T/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) SK3
T/T
mice was significantly less than that measured in WT or SK3 knockout control (SK3
DOX
) 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 SK3
T/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.
Details
- Title: Subtitle
- Overexpression of SK3 Channels Dampens Uterine Contractility to Prevent Preterm Labor in Mice
- Creators
- Stephanie L Pierce - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Jessica D.K Kresowik - Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Kathryn G Lamping - Department of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Sarah K England - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Biology of reproduction, Vol.78(6), pp.1058-1063
- DOI
- 10.1095/biolreprod.107.066423
- PMID
- 18305226
- PMCID
- PMC2930016
- ISSN
- 0006-3363
- eISSN
- 1529-7268
- Language
- English
- Date published
- 06/2008
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Obstetrics and Gynecology; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984094726702771
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