Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise

Cara C Rada; Stephanie L Pierce; Daniel W Nuno; Kathy Zimmerman; Kathryn G Lamping; Noelle C Bowdler; Robert M Weiss; Sarah K England

doi:10.1152/ajpendo.00165.2012

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Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise

Journal article

Open access

Peer reviewed

Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise

Cara C Rada, Stephanie L Pierce, Daniel W Nuno, Kathy Zimmerman, Kathryn G Lamping, Noelle C Bowdler, Robert M Weiss and Sarah K England

American journal of physiology: endocrinology and metabolism, Vol.303(7), pp.E825-831

10/01/2012

DOI: 10.1152/ajpendo.00165.2012

PMCID: PMC3469615

PMID: 22785240

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Abstract

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.

Pregnancy

Animals

Female

Fetal Death - genetics

Fetal Death - metabolism

Fetal Growth Retardation - genetics

Fetal Growth Retardation - metabolism

Heart Rate - genetics

Heart Rate - physiology

Male

Mice

Mice, Inbred C57BL

Mice, Transgenic

Organ Size

Placenta - anatomy & histology

Placenta - diagnostic imaging

Small-Conductance Calcium-Activated Potassium Channels - biosynthesis

Small-Conductance Calcium-Activated Potassium Channels - genetics

Stroke Volume - genetics

Stroke Volume - physiology

Ultrasonography, Prenatal - methods

Uterine Artery - anatomy & histology

Uterine Artery - diagnostic imaging

Uterus - blood supply

Uterus - diagnostic imaging

Details

Title: Subtitle: Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise
Creators: Cara C Rada - Department of Obstetrics and Gynecology, Washington Univ. School of Medicine, St. Louis, MO 63110, USA
Stephanie L Pierce
Daniel W Nuno - University of Iowa, Internal Medicine
Kathy Zimmerman - University of Iowa, Internal Medicine
Kathryn G Lamping - University of Iowa, Cardiovascular Medicine
Noelle C Bowdler - University of Iowa, Obstetrics and Gynecology
Robert M Weiss - University of Iowa, Cardiovascular Medicine
Sarah K England
Resource Type: Journal article
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.303(7), pp.E825-831
DOI: 10.1152/ajpendo.00165.2012
PMID: 22785240
PMCID: PMC3469615
NLM abbreviation: Am J Physiol Endocrinol Metab
ISSN: 0193-1849
eISSN: 1522-1555
Grant note: UL1 RR024979 / NCRR NIH HHS UL1 RR024979-03S3 / NCRR NIH HHS R01 HD-037831 / NICHD NIH HHS S10RR026293 / NCRR NIH HHS
Language: English
Date published: 10/01/2012
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Obstetrics and Gynecology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9983557405102771

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