| Expression of stretch-activated two-pore potassium channels in human myometrium in pregnancy and labor. | |
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MedLine Citation:
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PMID: 20811500 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Iain L O Buxton; Cherie A Singer; Jennifer N Tichenor |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-25 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e12372 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, School of Medicine, University of Nevada, Reno, Nevada, United States of America. ibuxton@medicine.nevada.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Female Gene Expression Regulation* / drug effects Humans 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* Pregnancy Premature Birth / genetics, metabolism, physiopathology Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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HD053028/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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