Document Detail

Expression of stretch-activated two-pore potassium channels in human myometrium in pregnancy and labor.
MedLine Citation:
PMID:  20811500     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: We tested the hypothesis that the stretch-activated, four-transmembrane domain, two pore potassium channels (K2P), TREK-1 and TRAAK are gestationally-regulated in human myometrium and contribute to uterine relaxation during pregnancy until labor.
METHODOLOGY: We determined the gene and protein expression of K2P channels in non-pregnant, pregnant term and preterm laboring myometrium. We employed both molecular biological and functional studies of K2P channels in myometrial samples taken from women undergoing cesarean delivery of a fetus.
PRINCIPAL FINDINGS: TREK-1, but not TREK-2, channels are expressed in human myometrium and significantly up-regulated during pregnancy. Down-regulation of TREK-1 message was seen by Q-PCR in laboring tissues consistent with a role for TREK-1 in maintaining uterine quiescence prior to labor. The TRAAK channel was unregulated in the same women. Blockade of stretch-activated channels with a channel non-specific tarantula toxin (GsMTx-4) or the more specific TREK-1 antagonist L-methionine ethyl ester altered contractile frequency in a dose-dependent manner in pregnant myometrium. Arachidonic acid treatment lowered contractile tension an effect blocked by fluphenazine. Functional studies are consistent with a role for TREK-1 in uterine quiescence.
CONCLUSIONS: We provide evidence supporting a role for TREK-1 in contributing to uterine quiescence during gestation and hypothesize that dysregulation of this mechanism may underlie certain cases of spontaneous pre-term birth.
Iain L O Buxton; Cherie A Singer; Jennifer N Tichenor
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-25
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-11-04     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e12372     Citation Subset:  IM    
Department of Pharmacology, School of Medicine, University of Nevada, Reno, Nevada, United States of America.
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MeSH Terms
Gene Expression Regulation* / drug effects
Labor, Obstetric / genetics*,  metabolism*,  physiology
Muscle Relaxation* / drug effects
Myometrium / drug effects,  metabolism*,  physiology
Potassium Channel Blockers / pharmacology
Potassium Channels / genetics,  metabolism*
Potassium Channels, Tandem Pore Domain / genetics,  metabolism*
Premature Birth / genetics,  metabolism,  physiopathology
Young Adult
Grant Support
Reg. No./Substance:
0/KCNK4 protein, human; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/Potassium Channels, Tandem Pore Domain; 0/potassium channel protein TREK-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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