Expression of stretch-activated two-pore potassium channels in human myometrium in pregnancy and labor.
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.


METHODS
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.


RESULTS
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.
Buxton
Iain L O
IL
Department of Pharmacology, School of Medicine, University of Nevada, Reno, Nevada, United States of America. ibuxton@medicine.nevada.edu
Singer
Cherie A
CA
Tichenor
Jennifer N
JN
D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007743:Labor, Obstetric / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
C503432:KCNK4 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1
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