Document Detail


Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise.
MedLine Citation:
PMID:  22785240     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The maternal cardiovascular system undergoes hemodynamic changes during pregnancy via angiogenesis and vasodilation to ensure adequate perfusion of the placenta. Improper vascularization at the maternal-fetal interface can cause pregnancy complications and poor fetal outcomes. Recent evidence indicates that small conductance Ca(2+)-activated K(+) channel subtype 3 (SK3) contributes to vascular remodeling during pregnancy, and we hypothesized that abnormal SK3 channel expression would alter the ability of the maternal cardiovascular system to adapt to pregnancy demands and lead to poor fetal outcomes. We investigated this hypothesis using transgenic Kcnn3(tm1Jpad)/Kcnn3(tm1Jpad) (SK3(T/T)) mice that overexpress the channel. Isolated pressurized uterine arteries from nonpregnant transgenic SK3(T/T) mice had larger basal diameters and decreased agonist-induced constriction than those from their wild-type counterparts; however, non-receptor-mediated depolarization remained intact. In addition to vascular changes, heart rates and ejection fraction were increased, whereas end systolic volume was reduced in SK3(T/T) mice compared with their wild-type littermates. Uterine sonography of the fetuses on pregnancy day 14 showed a significant decrease in fetal size in SK3(T/T) compared with wild-type mice; thus, SK3(T/T) mice displayed an intrauterine growth-restricted phenotype. The SK3(T/T) mice showed decreased placental thicknesses and higher incidence of fetal loss, losing over half of their complement of pups by midgestation. These results establish that the SK3 channel contributes to both maternal and fetal outcomes during pregnancy and point to the importance of SK3 channel regulation in maintaining a healthy pregnancy.
Authors:
Cara C Rada; Stephanie L Pierce; Daniel W Nuno; Kathy Zimmerman; Kathryn G Lamping; Noelle C Bowdler; Robert M Weiss; Sarah K England
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-07-11
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  303     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-01-07     Revised Date:  2013-10-11    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E825-31     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, Washington Univ. School of Medicine, St. Louis, MO 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Fetal Death / genetics,  metabolism*
Fetal Growth Retardation / genetics,  metabolism*
Heart Rate / genetics,  physiology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Organ Size
Placenta / anatomy & histology,  ultrasonography
Pregnancy
Small-Conductance Calcium-Activated Potassium Channels / biosynthesis*,  genetics
Stroke Volume / genetics,  physiology
Ultrasonography, Prenatal / methods
Uterine Artery / anatomy & histology,  ultrasonography
Uterus / blood supply,  ultrasonography
Grant Support
ID/Acronym/Agency:
R01 HD-037831/HD/NICHD NIH HHS; S10RR026293/RR/NCRR NIH HHS; UL1 RR024979-03S3/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Kcnn3 protein, mouse; 0/Small-Conductance Calcium-Activated Potassium Channels
Comments/Corrections

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